Systems, devices and methods for performing medical procedures in the intestine

ABSTRACT

A method for performing a medical procedure in an intestine of a patient is provided. The method comprises providing a system comprising: a catheter for insertion into the intestine, the catheter comprising: an elongate shaft comprising a distal portion; and a functional assembly positioned on the shaft distal portion and comprising at least one treatment element. The catheter is introduced into the patient, and target tissue is treated with the at least one treatment element. The target tissue comprises mucosal tissue of the small intestine, and the medical procedure can be configured to treat at least one of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of (1) International PatentApplication No. PCT/US2016/040512 , filed Jun. 30, 2016, which claimspriority to Provisional No. 62/187,594 , filed Jul. 1, 2015, and (2)International Patent Application Serial Number PCT/US2015/040775,entitled “Methods and Systems for Treating Diabetes and Related Diseasesand Disorders”, filed Jul. 16, 2015, which claims priority toProvisional No. 62/025,307 , filed Jul. 16, 2014, the entire content ofeach of which are incorporated herein by reference in their entity; thisapplication also claims the benefit of U.S. Provisional Application No.62/273,015 , entitled “Methods and Systems for Treating Diabetes,Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Steatohepatitis andRelated Diseases and Disorders”, filed Dec. 30, 2015, the entire contentof which is incorporated herein by reference in its entity.

This application is related to: U.S. patent application Ser. No.13/945,138, entitled “Devices and Methods for the Treatment of Tissue”,filed Jul. 18, 2013; U.S. patent application Ser. No. 14/470,503,entitled “Heat Ablation Systems, Devices and Methods for the Treatmentof Tissue”, filed Aug. 27, 2014; U.S. patent application Ser. No.14/515,324, entitled “Tissue Expansion Devices, Systems and Methods”,filed Oct. 15, 2014; U.S. patent application Ser. No. 14/609,332,entitled “Electrical Energy Ablation Systems, Devices and Methods forthe Treatment of Tissue”, filed Jan. 29, 2015; U.S. patent applicationSer. No. 14/609,334, entitled “Ablation Systems, Devices and Methods forthe Treatment of Tissue”, filed Jan. 29, 2015; U.S. patent applicationSer. No. 14/673,565, entitled “Methods, Systems and Devices forPerforming Multiple Treatments on a Patient”, filed Mar. 30, 2015; U.S.patent application Ser. No. 14/956,710, entitled “Methods, Systems andDevices for Reducing the Luminal Surface Area of the GastrointestinalTract”, filed Dec. 2, 2015; U.S. patent application Ser. No. 14/917,243,entitled “Systems, Methods and Devices for Treatment of Target Tissue”,filed Mar. 7, 2016; U.S. patent application Ser. No. 15/156,585,entitled “Systems, Devices and Methods for the Creation of a TherapeuticRestriction in the Gastrointestinal Tract”, filed May 17, 2016;International Patent Application Serial Number PCT/US2015/022293,entitled “Injectate Delivery Devices, Systems and Methods”, filed Mar.24, 2015, the entire contents of each of which are incorporated hereinby reference in their entirety for all purposes.

TECHNICAL FIELD

The embodiments disclosed herein relate generally to systems, devicesand methods for performing medical procedures in the intestine of apatient.

BACKGROUND OF THE INVENTION

Numerous diagnostic and therapeutic procedures are performed in thesmall and large intestine, as well as other locations of thegastrointestinal tract. Devices used in these procedures can bedifficult to maneuver and otherwise operate, and have limitedfunctionality There is a need for improved systems and devices fortreating and diagnosing tissue of the intestine, as well as a need formethods of treating intestinal tissue as a new or improved therapy forvarious diseases and disorders.

BRIEF SUMMARY OF THE INVENTION

According to one aspect of the present inventive concepts, a method forperforming a medical procedure in an intestine of a patient, comprising:providing a system comprising: a catheter for insertion into theintestine, the catheter comprising: an elongate shaft comprising adistal portion; and a functional assembly positioned on the shaft distalportion and comprising at least one treatment element; introducing thecatheter into the patient; and treating target tissue with the at leastone treatment element, wherein the target tissue comprises mucosaltissue of the small intestine; wherein the medical procedure isconfigured to treat at least one of non-alcoholic fatty liver disease(NAFLD) or non-alcoholic steatohepatitis (NASH).

In some embodiments, the medical procedure is further configured totreat insulin resistance.

In some embodiments, the medical procedure is further configured totreat a disease or disorder selected from the group consisting of: Type2 diabetes; Type 1 diabetes; “Double diabetes”; gestational diabetes;hyperglycemia; pre-diabetes; impaired glucose tolerance; insulinresistance; and combinations thereof.

In some embodiments, the system further comprises a console operablyattached to the functional assembly, and wherein the console comprisesone or more variable console parameters used to control the functionalassembly.

In some embodiments, the system further comprises at least one sensorconstructed and arranged to produce a sensor signal, and wherein themethod further comprises adjusting at least one variable consoleparameter based on the sensor signal. The console can be configured toperform closed-loop energy delivery to the functional assembly based onthe sensor signal.

In some embodiments, the treating target tissue modifies at least one ofnutrient absorption by the target tissue or hormonal signaling from thetarget tissue.

In some embodiments, the treating target tissue modifies secretions ofthe target tissue.

In some embodiments, the treating target tissue comprises treatingmucosal tissue within 15 cm of the ampulla of Vater.

In some embodiments, the method comprises avoiding treating tissuebetween a first location proximate the ampulla of Vater and a secondlocation 0.5 cm distal to the ampulla of Vater.

In some embodiments, at least 6 cm, or at least 9 cm of length ofduodenum are treated.

In some embodiments, the treating target tissue comprises treating atleast a first axial segment and a second axial segment of the intestine.The treating target tissue can comprise treating between two and sixaxial segments of the intestine to treat at least 6 cm of axial lengthof intestine.

In some embodiments, the treating target tissue comprises treating anamount of tissue that is based on the severity of the patient's NAFLDand/or NASH.

In some embodiments, the method further comprises identifying non-targettissue. The non-target tissue can be identified by marking tissueselected from the group consisting of: ampulla of Vater; tissueproximate the ampulla of Vater; pylorus; tissue proximate the pylorus;and combinations thereof.

In some embodiments, the treating target tissue comprises a series oftissue ablation steps, each comprising ablation of an axial length ofintestinal tissue, wherein each ablation step is preceded by a tissueexpansion step. The method can further comprise preventing axial motionof the functional assembly between the tissue expansion and the tissuetreatment steps. The method can further comprise applying vacuum totissue during the tissue expansion step. The tissue expansion cancomprise delivering injectate into submucosal tissue, and the injectatecan comprise visualizable material.

In some embodiments, the treating target tissue comprises a series oftissue ablation steps, each ablation step comprising ablation of anaxial length of intestinal tissue, wherein each ablation step isfollowed by a tissue neutralizing step. Each ablation step can comprisea heat ablation of tissue, and each neutralizing step can comprise acooling of tissue. The method can further comprise performing a separatetissue neutralizing step prior to each ablation step. Each ablation stepcan comprise a heat ablation of tissue, and each separate neutralizingstep can comprise a cooling of tissue.

In some embodiments, the method further comprises maintaining thefunctional assembly at or below a target diameter.

In some embodiments, the method further comprises maintaining thefunctional assembly at or below a target pressure.

In some embodiments, the method further comprises maintaining thefunctional assembly at or below a target volume.

In some embodiments, the method further comprises delivering ananti-peristaltic agent.

In some embodiments, the method further comprises modifying the pressureof a segment of intestine that is proximate the target tissue beingtreated.

In some embodiments, the functional assembly includes a tissuecontacting portion comprising a surface area between 500 mm² and 3500mm².

In some embodiments, the functional assembly comprises an expandeddiameter between 19 mm and 28 mm.

In some embodiments, the functional assembly comprises at least onefluid delivery element.

In some embodiments, the functional assembly further comprises at leastone recess. The functional assembly can further comprise a vacuum portpositioned in the at least one recess.

In some embodiments, the catheter further comprises a fluid removal portconfigured to remove fluid from a segment of the intestine.

According to one aspect of the present inventive concepts, a system forperforming a medical procedure in an intestine of a patient comprises afirst catheter for insertion into the intestine, the first cathetercomprising an elongate shaft comprising a distal portion, and afunctional assembly positioned on the shaft distal portion andcomprising at least one functional element. The system further comprisesa console operably attachable to the first catheter functional assemblyand comprising one or more variable console settings used to control thefunctional assembly, and at least one sensor constructed and arranged toproduce a sensor signal, and at least one console setting is configuredto be adjusted based on the sensor signal.

In some embodiments, the sensor signal is related to a physiologicparameter of the intestine. The sensor signal can be related to theanatomical geometry of a portion of the intestine. The sensor signal canbe related to force applied to tissue of the intestine. The sensorsignal can be related to pressure applied to tissue of the intestine.The sensor signal can be related to temperature of tissue of theintestine.

In some embodiments, the sensor signal is related to a parameter of thefunctional assembly. The sensor signal can be related to pressure withinthe functional assembly. The sensor signal can be related to forceapplied to a portion of the functional assembly. The sensor signal canbe related to the temperature of at least a portion of the functionalassembly. The sensor signal can be related to the temperature of fluidwithin the functional assembly.

In some embodiments, the system is configured to maintain pressurewithin the functional assembly relative to a threshold based on thesensor signal. The system can be configured to maintain pressure withinthe functional assembly below a pressure threshold, above a pressurethreshold and/or within a range of pressures based on the sensor signal.The system can be configured to maintain the pressure relative to athreshold during a tissue ablation procedure. The system can beconfigured to maintain the pressure relative to a threshold during atissue expansion procedure. The system can be configured to inflate thefunctional assembly to a first pressure, deliver injectate into tissue,and reduce the pressure in the functional assembly when the pressure inthe functional assembly reaches a threshold. The first pressure cancomprise a pressure of approximately 0.7 psi and the threshold cancomprise a pressure of approximately 0.9 psi.

In some embodiments, the console settings comprise a parameter selectedfrom the group consisting of: delivery rate of fluid into the functionalassembly; withdrawal rate of fluid from the functional assembly;delivery rate of fluid into tissue; rate of energy delivered intotissue; peak energy level delivered into tissue; average energy deliveryrate delivered into tissue; amount of energy delivered into tissueduring a time period; temperature of an ablative fluid; temperature of aneutralizing fluid; temperature of functional assembly; pressure offunctional assembly; pressure of fluid delivered into functionalassembly; pressure of fluid delivered into tissue; duration of energydelivery; time of energy delivery (e.g. time of day of or relative timecompared to another step); translation rate; translation rate of thefunctional assembly; rotation rate; rotation rate of the functionalassembly; a flow rate; a recirculation rate; a heating rate; a heatingtemperature; a cooling rate; a cooling temperature; a sampling rate; asensor sampling rate; and combinations thereof.

In some embodiments, the console settings comprise a system parameterselected from the group consisting of: pressure and/or volume of a fluiddelivered to the elongate shaft; pressure and/or volume of a fluiddelivered to and/or extracted from the functional assembly; pressureand/or volume of a fluid delivered to one or more conduits of theelongate shaft; pressure and/or volume of a fluid within one or moreconduits of the elongate shaft; level of a vacuum within a conduit ofthe elongate shaft; a force used to advance and/or retract one or moreconduits of the elongate shaft; a force used to advance and/or retractone or more fluid delivery elements of the first catheter; andcombinations thereof.

In some embodiments, the console settings comprise a system parameterselected from the group consisting of: temperature, flow rate, pressureand/or duration of fluid delivered to the first catheter and/or thefunctional assembly; temperature, flow rate, pressure and/or duration offluid contained within the functional assembly and/or recirculating toand/or from the functional assembly: and combinations thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of embodimentsof the present inventive concepts will be apparent from the moreparticular description of preferred embodiments, as illustrated in theaccompanying drawings in which like reference characters refer to thesame or like elements. The drawings are not necessarily to scale,emphasis instead being placed upon illustrating the principles of thepreferred embodiments.

FIG. 1 is a schematic view of a system for performing a medicalprocedure in the intestine of a patient, consistent with the presentinventive concepts.

FIG. 2 is a schematic view of a system and device for performing amedical procedure on the small intestine of a patient, consistent withthe present inventive concepts.

FIG. 3 is an anatomic view of a system for performing a medicalprocedure comprising a catheter and a sheath for inserting the catheterinto the intestine of the patient, consistent with the present inventiveconcepts.

FIGS. 3A and 3B are side sectional and end sectional views,respectively, of the distal portion of a sheath, without an insertedcatheter or guidewire, consistent with the present inventive concepts.

FIGS. 4A, 4B and 4C are anatomical, side sectional views of a series ofsteps for performing a medical procedure, consistent with the presentinventive concepts.

FIGS. 5A and 5B are end and side views of the distal portion of acatheter including recessed ports, shaft-located vacuum ports, and aninflatable distal tip, consistent with the present inventive concepts.

FIGS. 6A and 6B are anatomical, side sectional views of the distal endof a catheter comprising a functional assembly configured to expand tomultiple geometric configurations, consistent with the present inventiveconcepts.

FIG. 7 is an anatomical, side sectional view of the distal end of acatheter comprising a functional assembly including a balloon withvaried wall thickness, consistent with the present inventive concepts.

FIG. 8 is an anatomical, side sectional view of the distal end of acatheter comprising a functional assembly including an insulatingelement, consistent with the present inventive concepts.

FIG. 9 is a side view of a catheter comprising a tissue dissectingassembly, consistent with the present inventive concepts.

FIG. 9A is a magnified view of one of the tools of FIG. 9, consistentwith the present inventive concepts.

FIGS. 10A-D are side views of a distal portion of a system including asheath with a sealing distal end, consistent with the present inventiveconcepts.

FIG. 11 is a side view of the distal portion of a catheter includingmultiple shafts arranged in a helix, consistent with the presentinventive concepts.

FIG. 12 is a side view of a distal portion of a catheter comprisingports mounted on a tapered proximal portion of a functional assembly,consistent with the present inventive concepts.

FIG. 13 is a side view of a distal portion of a catheter comprisingneedle-directing ports mounted on a proximal end of a functionalassembly, consistent with the present inventive concepts.

FIG. 14 is a side sectional view of a distal portion of a cathetercomprising a functional assembly including an inner and outer balloon,consistent with the present inventive concepts.

FIG. 15 is an end sectional view of a distal portion of a cathetercomprising a functional assembly including two partial circumferentialballoons, consistent with the present inventive concepts.

FIG. 16 is a side sectional view of a distal portion of a cathetercomprising a functional assembly including an inner chamber and an outerballoon, consistent with the present inventive concepts.

FIGS. 17A-B are two anatomical, side sectional views of a distal portionof a catheter comprising a functional assembly and at least onestabilizing assembly, consistent with the present inventive concepts.

FIG. 18 is an anatomical, side sectional view of a distal portion of acatheter comprising a functional assembly configured to avoid unintendedtranslation within the intestine, consistent with the present inventiveconcepts.

FIG. 19 is an anatomical, side sectional view of a distal portion of asystem and catheter comprising a functional assembly including one ormore reflective surfaces, consistent with the present inventiveconcepts.

FIG. 20 is a side sectional view of a distal portion of a cathetercomprising a functional assembly attached to at least two fluidconduits, consistent with the present inventive concepts.

FIG. 21 is a side sectional view of a distal portion of a cathetercomprising a functional assembly including one or more light deliveryelements, consistent with the present inventive concepts.

FIG. 22 is a side view of a distal portion of a catheter comprising afunctional assembly comprising a first expanding element and a secondexpanding element, consistent with the present inventive concepts.

FIG. 23 is a side sectional view of a distal portion of a cathetercomprising an inner balloon configured to ablate and an outer balloonconfigured to position, consistent with the present inventive concepts.

FIG. 24 is a side view of a distal portion of a catheter comprising afunctional assembly including a first expanding element and a secondexpanding element, consistent with the present inventive concepts.

FIGS. 25A-C are anatomical, side sectional views of the distal portionof a multiple expandable assembly catheter in a series of steps,consistent with the present inventive concepts.

FIG. 26 is a side sectional view of an anchorable guidewire, consistentwith the present inventive concepts.

FIG. 26A is a side sectional view of the proximal portion of aguidewire, with an expansion tool attached about the valve assembly,consistent with the present inventive concepts.

FIG. 27 is a medical device shaft comprising a tapered profile,consistent with the present inventive concepts.

FIG. 28 is a medical device shaft comprising a varied pitch braid,consistent with the present inventive concepts.

FIGS. 29A-D is a camera view of a series of steps for expanding tissueand treating target tissue at a single axial segment, consistent withthe present inventive concepts.

FIGS. 30A-B are side sectional views of a distal portion of a cathetercomprising a tissue-engaging fluid delivery element, consistent with thepresent inventive concepts.

FIG. 31 is a medical device shaft comprising one or more insulatingelements, consistent with the present inventive concepts.

FIG. 32 is an end sectional view of a system comprising a catheter witha non-circular cross section and a body introduction device with acircular cross section, consistent with the present inventive concepts.

FIG. 33 is an end sectional view of a system comprising a catheter witha functional assembly comprising a non-circular unexpanded cross sectionand a body introduction device with a circular cross section, consistentwith the present inventive concepts.

FIG. 34 is a flowchart of a method of performing a medical procedureincluding gathering sensor information, consistent with the presentinventive concepts.

FIG. 35 is a flowchart of a method of performing a medical procedureincluding performing a tissue expansion with a functional assembly, andtreating target tissue with the same or a different functional assembly,consistent with the present inventive concepts.

FIG. 36 is a flowchart of a method of performing a medical procedureincluding expanding a functional assembly to a non-contactingconfiguration, and subsequently collapsing the intestine around thefunctional assembly, consistent with the present inventive concepts.

FIG. 37 is a flowchart of a method of performing a medical procedureincluding ablating tubular tissue proximate expanded tissue, includingperforming the ablation based on one or more pre-tissue-expansiondiameters and/or one or more post-tissue-expansion diameters, consistentwith the present inventive concepts.

FIG. 38 is a flowchart of a method of expanding a functional assembly intwo discrete steps, consistent with the present inventive concepts.

FIG. 39 is a flowchart of a method of expanding a functional assemblybased on two pressure thresholds, consistent with the present inventiveconcepts.

FIG. 40 is a flowchart of a method of causing a functional assembly tocontact wall tissue of a segment of the intestine, consistent with thepresent inventive concepts.

FIG. 41 is a flowchart of a method of performing a tissue treatment thatincludes activating a functional assembly based on an image, consistentwith the present inventive concepts.

FIG. 42 is a flowchart of a method of performing a tissue treatmentbased on the geometry of the intestine, consistent with the presentinventive concepts.

FIG. 43 is a flowchart of a method of marking tissue and performing atissue treatment based on the tissue marking, consistent with thepresent inventive concepts.

FIGS. 44-62 are graphs representing the results of early human clinicalstudies conducted by the applicant, and associated data collected,consistent with the present inventive concepts.

DETAILED DESCRIPTION OF THE DRAWINGS

The terminology used herein is for the purpose of describing particularembodiments and is not intended to be limiting of the inventiveconcepts. Furthermore, embodiments of the present inventive concepts mayinclude several novel features, no single one of which is solelyresponsible for its desirable attributes or which is essential topracticing an inventive concept described herein. As used herein, thesingular forms “a,” “an” and “the” are intended to include the pluralforms as well, unless the context clearly indicates otherwise.

It will be further understood that the words “comprising” (and any formof comprising, such as “comprise” and “comprises”), “having” (and anyform of having, such as “have” and “has”), “including” (and any form ofincluding, such as “includes” and “include”) or “containing” (and anyform of containing, such as “contains” and “contain”) when used herein,specify the presence of stated features, integers, steps, operations,elements, and/or components, but do not preclude the presence oraddition of one or more other features, integers, steps, operations,elements, components, and/or groups thereof.

It will be understood that, although the terms first, second, third etc.may be used herein to describe various limitations, elements,components, regions, layers and/or sections, these limitations,elements, components, regions, layers and/or sections should not belimited by these terms. These terms are only used to distinguish onelimitation, element, component, region, layer or section from anotherlimitation, element, component, region, layer or section. Thus, a firstlimitation, element, component, region, layer or section discussed belowcould be termed a second limitation, element, component, region, layeror section without departing from the teachings of the presentapplication.

It will be further understood that when an element is referred to asbeing “on”, “attached”, “connected” or “coupled” to another element, itcan be directly on or above, or connected or coupled to, the otherelement, or one or more intervening elements can be present. Incontrast, when an element is referred to as being “directly on”,“directly attached”, “directly connected” or “directly coupled” toanother element, there are no intervening elements present. Other wordsused to describe the relationship between elements should be interpretedin a like fashion (e.g., “between” versus “directly between,” “adjacent”versus “directly adjacent,” etc.).

It will be further understood that when a first element is referred toas being “in”, “on” and/or “within” a second element, the first elementcan be positioned: within an internal space of the second element,within a portion of the second element (e.g. within a wall of the secondelement); positioned on an external and/or internal surface of thesecond element; and combinations of one or more of these.

Spatially relative terms, such as “beneath,” “below,” “lower,” “above,”“upper” and the like may be used to describe an element and/or feature'srelationship to another element(s) and/or feature(s) as, for example,illustrated in the figures. It will be understood that the spatiallyrelative terms are intended to encompass different orientations of thedevice in use and/or operation in addition to the orientation depictedin the figures. For example, if the device in a figure is turned over,elements described as “below” and/or “beneath” other elements orfeatures would then be oriented “above” the other elements or features.The device can be otherwise oriented (e.g., rotated 90 degrees or atother orientations) and the spatially relative descriptors used hereininterpreted accordingly.

The term “and/or” where used herein is to be taken as specificdisclosure of each of the two specified features or components with orwithout the other. For example “A and/or B” is to be taken as specificdisclosure of each of (i) A, (ii) B and (iii) A and B, just as if eachis set out individually herein.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable sub-combination. For example, it will be appreciated thatall features set out in any of the claims (whether independent ordependent) can be combined in any given way.

As described herein, “room pressure” shall mean pressure of theenvironment surrounding the systems and devices of the present inventiveconcepts. Positive pressure includes pressure above room pressure orsimply a pressure that is greater than another pressure, such as apositive differential pressure across a fluid pathway component such asa valve. Negative pressure includes pressure below room pressure or apressure that is less than another pressure, such as a negativedifferential pressure across a fluid component pathway such as a valve.Negative pressure can include a vacuum but does not imply a pressurebelow a vacuum. As used herein, the term “vacuum” can be used to referto a full or partial vacuum, or any negative pressure as describedhereabove. As used herein, the term “vacuum level” refers to a measureof a vacuum wherein the lower the pressure, the greater the vacuumlevel.

The term “diameter” where used herein to describe a non-circulargeometry is to be taken as the diameter of a hypothetical circleapproximating the geometry being described. For example, when describinga cross section, such as the cross section of a component, the term“diameter” shall be taken to represent the diameter of a hypotheticalcircle with the same cross sectional area as the cross section of thecomponent being described.

As used herein, the term “ablative temperature” refers to a temperatureat which tissue necrosis or other desired tissue treatment occurs (e.g.a temperature sufficiently hot or sufficiently cold to cause tissuenecrosis). As used herein, the term “ablative fluid” refers to one ormore liquids, gases, gels or other fluids whose thermal properties causetissue necrosis and/or another desired tissue treatment (e.g. one ormore fluids at an ablative temperature). Alternatively or additionally,“ablative fluid” refers to one or more fluids whose chemical properties(at room temperature, body temperature or otherwise) cause tissuenecrosis or another desired tissue treatment. A tissue treatment element(e.g. a functional element) of the present inventive concepts cancomprise one or more ablative fluids.

As used herein, the term “threshold” refers to a maximum level, aminimum level and/or range of values. In some embodiments, a systemparameter is maintained above a threshold, below a threshold and/orwithin a threshold, to cause a desired effect (e.g. efficacious therapy)and/or to prevent or otherwise reduce (hereinafter “prevent”) anundesired event (e.g. a device or clinical adverse event). In someembodiments, a system parameter is maintained above a first threshold(e.g. above a first temperature threshold) and below a second threshold(e.g. below a second temperature threshold). In some embodiments, athreshold value is determined to include a safety margin, such as tocause a desired effect and/or prevent an undesired event as the systemparameter slightly crosses the threshold (e.g. to account for patientvariability, system variability, tolerances, and the like).

As used herein, the term “proximate”, when used to describe proximity ofa first component or location to a second component or location, is tobe taken to include one or more locations near to the second componentor location, as well as locations in, on and/or within the secondcomponent or location. For example, a component positioned proximate ananatomical site (e.g. a target tissue location), shall includecomponents positioned near to the anatomical site, as well as componentspositioned in, on and/or within the anatomical site.

As used herein, the term “functional element” is to be taken to includeone or more elements constructed and arranged to perform a function. Insome embodiments, a functional element is configured to deliver energyand/or otherwise treat tissue (e.g. a functional element configured as atreatment element). Alternatively or additionally, a functional elementcan be configured to record one or more parameters, such as a patientphysiologic parameter; a patient anatomical parameter (e.g. a tissuegeometry parameter); a patient environment parameter; and/or a systemparameter. In some embodiments, a functional element comprises one ormore elements constructed and arranged to perform a function selectedfrom the group consisting of: deliver energy; extract energy (e.g. tocool a component); deliver a drug or other agent; manipulate a systemcomponent or patient tissue; record or otherwise sense a parameter suchas a patient physiologic parameter or a patient anatomical parameter;and combinations of one or more of these. A functional element cancomprise a fluid, such as an ablative fluid (as described hereabove)comprising a liquid or gas configured to ablate or otherwise treattissue. A functional element can comprise a reservoir, such as anexpandable balloon configured to receive an ablative fluid. A“functional assembly” can comprise an assembly constructed and arrangedto perform a function, such as is described hereabove. In someembodiments, a functional assembly is configured to deliver energyand/or otherwise treat tissue (e.g. a functional assembly configured asa treatment assembly). Alternatively or additionally, a functionalassembly can be configured to record one or more parameters, such as apatient physiologic parameter; a patient anatomical parameter; a patientenvironment parameter; and/or a system parameter. A functional assemblycan comprise an expandable assembly. A functional assembly can compriseone or more functional elements.

As used herein, the term “transducer” is to be taken to include anycomponent or combination of components that receives energy or anyinput, and produces an output. For example, a transducer can include anelectrode that receives electrical energy, and distributes theelectrical energy to tissue (e.g. based on the size of the electrode).In some configurations, a transducer converts an electrical signal intoany output, such as light (e.g. a transducer comprising a light emittingdiode or light bulb), sound (e.g. a transducer comprising a piezocrystal configured to deliver ultrasound energy), pressure, heat energy,cryogenic energy, chemical energy; mechanical energy (e.g. a transducercomprising a motor or a solenoid), magnetic energy, and/or a differentelectrical signal. Alternatively or additionally, a transducer canconvert a physical quantity (e.g. variations in a physical quantity)into an electrical signal. A transducer can include any component thatdelivers energy and/or an agent to tissue, such as a transducerconfigured to deliver one or more of: heat energy to tissue; cryogenicenergy to tissue; electrical energy to tissue (e.g. a transducercomprising one or more electrodes); light energy to tissue (e.g. atransducer comprising a laser, light emitting diode and/or opticalcomponent such as a lens or prism); mechanical energy to tissue (e.g. atransducer comprising a tissue manipulating element); sound energy totissue (e.g. a transducer comprising a piezo crystal); chemical energy;electromagnetic energy; magnetic energy; and combinations of one or moreof these. Alternatively or additionally, a transducer can comprise amechanism, such as a valve, a grasping element; an anchoring mechanism;an electrically-activated mechanism, a mechanically-activated mechanismand/or a thermally activated mechanism.

As used herein, the term “tissue contacting surface” refers to a surfaceof a system or device component that makes physical contact with tissue,such as a portion of an external surface of an expandable component(e.g. a portion of a balloon's surface) which contacts tissue onceexpanded. In some embodiments, tissue contacting a tissue contactingsurface directly receives energy from the tissue contacting surface ofthe expandable components, however tissue in proximity (e.g. below oralongside) also receives energy (e.g. via conduction of the deliveredenergy and/or a resultant heat energy).

It is an object of the present inventive concepts to provide systems,methods and devices for safely and effectively treating and/ordiagnosing a volume of tissue (the “target tissue”), such as to treatand/or diagnose a patient disease or disorder. Target tissue cancomprise one or more target tissue segments or other target tissueportions, such as target tissue located in the intestine of a patient.Clinical procedures in the duodenum and other locations of the smallintestine are challenging for a number of reasons, such as those causedby the long distance between the mouth and the intestine and thecomplexities of the gastrointestinal passageway encountered (includingpassage through the stomach) during device (e.g. catheter) insertion andoperation. Intestinal diameter varies along its length, and effectivedevices must accommodate this variation. The intestine is quitedistensible in the longitudinal and radial directions, furthercomplicating device (e.g. catheter) manipulation and operation (e.g.delivery of energy to tissue). Mobility of intestinal mucosa relative tomuscularis is present, as well as mobility of the full wall, but canresult in undesired stretching, compression and intussusception. Theduodenum is normally closed, and requires insufflation to open (e.g. forvisualization). The insufflation medium (e.g. gas) moves through theintestine, so more must be delivered, while excess gas causes discomfortor other adverse effect for the patient. Duodenal and other intestinaltissue tends to stretch or compress as a device is advanced orretracted, respectively, such as to cause retrograde expulsion ofdevices if a stabilization force is not maintained. It is difficult tomanipulate and control devices that include treatment and other elementspositioned in the small intestine. The small intestine wraps around thepancreas, and the curvature is quite variable from patient to patient.The length of the intestine along an outer curve is longer than thatalong an inner curve. In many procedures, there is a desire to avoiddamage to the ampulla of Vater (e.g. to avoid restricting bile and/orpancreatic fluid), tissue which can be difficult to visualize orotherwise identify. There are relatively few endoscopically visualizablelandmarks in the intestine, making it difficult to know where in theintestine a portion (e.g. a distal portion) of a device is positioned.Access to the intestine through the stomach via an over-the wirecatheter loses one-to-one motion between a proximal handle and a distalportion of the device, as slack can accumulate in the stomach duringadvancement and slack can be relieved from the stomach duringwithdrawal. Accessing the intestine can include entering the intestinethrough the pylorus, a small sphincter, from the stomach, and in obesepatients, large stretchable stomachs make it difficult to direct adevice to the pylorus. The intestinal mucosa has a very irregularsurface due to plicae circulares and mucosal villi, and performing atreatment (e.g. an ablation treatment) of the intestinal mucosa is quitedifferent from a treatment procedure performed in the stomach oresophagus, because of this irregularity. Peristalsis present in thesmall intestine is dynamic and unpredictable and can alter functionalelement, functional assembly and/or other device component positionand/or contact level with tissue. The intestine is not only thin-walled,but the thickness of the wall is highly variable, even within smallaxial segments of the small intestine, thus complicating preferentialablation of inner layers versus outer layers of the small intestine. Themuscularis is innervated and scars and/or stenoses easily, and as such,even minimal trauma to the muscularis should be avoided.

Target tissue can comprise one or more layers of a portion of tubular ornon-tubular tissue, such as tissue of an organ or tissue of thegastrointestinal (GI) tract of a patient, such as tissue of the smallintestine or large intestine. The systems and devices of the presentinventive concepts can include one or more functional assemblies and/orfunctional elements configured to treat target tissue, such as atreatment element comprising fluid at an ablative temperature deliveredto a balloon (ablative temperature fluid and/or balloon filled withablative fluid each referred to singly or collectively as a “functionalelement” or a “treatment element” of the present inventive concepts).One or more functional elements can be provided in, on and/or within anexpandable functional assembly or other radially deployable mechanism.Functional assemblies and/or functional elements can be configured totreat target tissue (e.g. deliver energy to target tissue), such as tomodify target tissue (e.g. to modify the secretions from the targettissue and/or absorption of the target tissue), ablate target tissue(e.g. to cause the replacement of the target tissue with “new tissue”)and/or to cause a reduction in the surface area of target tissue (e.g.the luminal surface area of an inner wall of tubular tissue) at and/orproximate to one or more locations where the treatment was performed(e.g. at and/or proximate the location where energy was delivered). Theluminal or other tissue treatment can occur acutely and/or it can takeplace over time, such as days, weeks or months. A tissue surface areareduction can correspond to a reduction in mucosal surface areaavailable to function in an absorptive, neuronal signaling, and/or ahormonal secretory capacity. A target tissue treatment can result in thereplacement of target tissue with new tissue with different absorptiveand/or secretory capacity and/or other desirable effect related toreplacement and/or modification of target tissue. The treatment oftarget tissue with the systems, devices and methods of the presentinventive concepts can provide a therapeutic benefit to the patient,such as to treat one or more diseases or disorders of the patient, asdescribed in detail herebelow.

Each functional assembly (e.g. treatment assembly) can comprise at leastone functional element (e.g. tissue treatment element) such as a tissuetreatment element selected from the group consisting of: ablative fluiddelivered to a balloon or other expandable fluid reservoir; energydelivery element mounted to an expandable functional assembly such as anelectrode or other energy delivery element configured to deliverradiofrequency (RF) energy and/or microwave energy; light deliveryelement configured to deliver laser or other light energy; fluiddelivery element (e.g. needle or nozzle) configured to deliver ablativefluid directly onto and/or into tissue; sound delivery element such asan ultrasonic and/or subsonic sound delivery element; and combinationsof one or more of these. Numerous forms of functional assemblies and/orfunctional elements can be included. In some embodiments, the functionalassemblies and/or the one or more functional elements contained thereinare configured as described in: applicant's co-pending U.S. patentapplication Ser. No. 13/945,138, entitled “Devices and Methods for theTreatment of Tissue”, filed Jul. 18, 2013; applicant's co-pending U.S.patent application Ser. No. 14/470,503, entitled “Heat Ablation Systems,Devices and Methods for the Treatment of Tissue”, filed Aug. 27, 2014;applicant's co-pending U.S. patent application Ser. No. 14/609,332,entitled “Electrical Energy Ablation Systems, Devices and Methods forthe Treatment of Tissue”, filed Jan. 29, 2015; and/or applicant'sco-pending U.S. patent application Ser. No. 14/609,334, entitled“Ablation Systems, Devices and Methods for the Treatment of Tissue”,filed Jan. 29, 2015; the content of each of which is incorporated hereinby reference in its entirety for all purposes.

The treatment assemblies and/or treatment elements of the presentinventive concepts can be constructed and arranged to deliver one ormore treatments (e.g. deliver energy, deliver a chemically ablativefluid, mechanically abrade and/or otherwise treat tissue) directly to aparticular area of tissue, the “delivery zone”. During a single deliveryof treatment, a treatment element can be constructed and arranged todeliver treatment to a relatively continuous surface of tissue (e.g. acontinuous surface of tissue in contact with a balloon filled withablative fluid or a surface of tissue onto which a chemically ablativefluid is sprayed, coated or otherwise delivered). In thesecontinuous-surface treatment delivery embodiments, the delivery zonecomprises the continuous surface of tissue receiving the treatmentdirectly. Alternatively, a treatment element can be constructed andarranged to deliver treatment to multiple discrete portions of a tissuesurface, with one or more tissue surface portions in-between othersurface portions that do not directly receive energy or other treatmentfrom the treatment element. In these segmented-surface treatmentdelivery embodiments, the delivery zone is defined by a periphery of themultiple tissue surface area portions receiving treatment, similar to a“convex hull” or “convex envelope” used in mathematics to define an areaincluding a number of discrete locations that define a periphery. Adelivery zone can comprise two or more contiguous or non-contiguousdelivery zones, and multiple delivery zones can be treated sequentiallyand/or simultaneously.

For example, in embodiments where the treatment element is hot fluid(e.g. ablative fluid at a sufficiently high temperature to cause tissuenecrosis) positioned within a balloon, the delivery zone comprises alltissue surfaces contacted by the balloon that directly receive ablativethermal energy from the ablative fluid through the balloon. Inembodiments where the treatment element is a balloon filled with coldfluid (e.g. ablative fluid at a sufficiently low temperature to causetissue necrosis), the delivery zone can comprise all tissue surfacescontacted by the balloon that have heat directly extracted from them bythe cold fluid (e.g. at a sufficient cold temperature to treat thetissue). In embodiments where the treatment element is an array ofelectrodes configured to deliver electrical energy (e.g. RF energy) totissue, the delivery zone can comprise an area defined by the electrodeson the periphery of the array (e.g. a convex hull as described above),such as when the electrodes are positioned and energy is delivered totreat relatively the entire surface of tissue within the periphery. Inembodiments where the treatment element comprises one or more fluiddelivery elements delivering ablative fluid directly onto tissue (e.g.an ablative fluid whose chemical nature modifies tissue, at bodytemperature or otherwise), the delivery zone can comprise a surfacedefined by the periphery of tissue locations receiving the ablativefluid, such as when the ablative fluid is delivered (e.g. sprayed orotherwise applied, such as via a sponge) to relatively the entiresurface within the periphery. In embodiments where the treatment elementcomprises one or more light delivery elements such as those that deliverlaser energy to tissue, the delivery zone can comprise a surface areadefined by the periphery of tissue locations receiving the light energy,such as when light is delivered at a set of locations and with amagnitude of energy configured to treat relatively the entire surface oftissue within the periphery. In these embodiments, light can bedelivered to relatively the entire energy delivery zone, or to a largenumber (e.g. greater than 100) of tissue locations within the peripheryof the delivery zone (e g making up less than 50%, less than 20% or lessthan 10% of the total surface area of the delivery zone). In embodimentswhere the treatment element comprises one or more sound deliveryelements such as those that deliver sub-sonic and/or ultrasonic soundenergy to tissue, the delivery zone can comprise a surface area definedby the periphery of tissue locations receiving the sound energy, such aswhen ablative sound energy is delivered at a set of locations and with amagnitude of energy configured to treat relatively the entire surface oftissue within the periphery. In embodiments in which the treatmentelement comprises a mechanical cutter or other abrasion element, thedelivery zone can comprise a surface defined by all tissue dissected,cut, mechanically disrupted and/or otherwise modified during a singleabrading step of the mechanical abrader.

A delivery zone can comprise a cumulative set of delivery zones thatreceive treatment simultaneously and/or sequentially, by one or moretissue treatment elements, such as those described herein. A deliveryzone can comprise a first delivery zone defined when a treatment elementtreats target tissue in a first treatment delivery, plus a seconddelivery zone defined when the treatment element treats target tissue ina second treatment delivery, and so on. In these embodiments, thetreatment element can be translated, rotated and/or otherwiserepositioned between treatments (e.g. energy delivery), where eachdelivery zone is associated with the position of the treatment elementduring each treatment. Multiple delivery zones can receive treatment ina single procedure, such as within a period of less than twenty-fourhours. A delivery zone can comprise a set of multiple delivery zonestreated by two or more treatment elements.

Target tissue treated by each energy delivery and/or other treatmentdelivery comprises the tissue directly receiving treatment (i.e. thetissue defined by the delivery zone) plus “neighboring tissue” which isalso modified by the associated treatment delivery. The neighboringtissue can comprise tissue alongside, below (e.g. in a deeper tissuelayer) and/or otherwise proximate the delivery zone tissue. Theneighboring tissue treatment can be due to one or more of: conductionand/or convection of heat or cold from the delivery zone; flow ofablative fluid from the delivery zone; flow of toxins or other agentsthat occur during cell degradation and/or cell death; radiation;luminescence, light dissipation; and other energy and/or chemicalpropagation mechanisms. In some embodiments, an area (i.e. the deliveryzone) comprising an inner surface of mucosal tissue directly receivestreatment from one or more treatment elements (e.g. an ablative fluidcontained within a balloon), and the total volume of target tissuetreated by that single treatment delivery includes: the delivery zonetissue (i.e. surface mucosal tissue directly receiving energy and/orother treatment from the treatment element); surface mucosal tissue inclose proximity (e.g. adjacent) to the delivery zone tissue; and mucosaland potentially submucosal tissue layers beneath (deeper than) thedelivery zone tissue and the treated adjacent surface mucosal tissue.

In some embodiments, a “treatment neutralizing” procedure is performedafter one or more treatments (e.g. energy deliveries), such as atreatment neutralizing cooling procedure performed after one or moretreatment elements deliver heat to treat target tissue, or a treatmentneutralizing warming procedure performed after one or more treatmentelements deliver cryogenic energy to treat target tissue. In theseembodiments, the treatment neutralizing cooling or warming fluid can bedelivered to the same functional assembly (e.g. an expandable functionalassembly comprising a balloon) delivering the heat or cryogenictreatment, respectively, and/or the neutralizing fluid can be delivereddirectly to tissue by the same or different functional assembly orfunctional element. In some embodiments, a functional element deliversan ablating agent to target tissue (e.g. a chemical or other agentconfigured to cause target tissue necrosis or otherwise treat targettissue), and a treatment neutralizing procedure comprises delivery of aneutralizing agent (by the same or different functional element) totarget and/or non-target tissue to reduce continued ablation due to thedelivered caustic ablative fluid (e.g. a base to neutralize a deliveredacid or an acid to neutralize a delivered base).

Each functional assembly and/or functional element of the presentinventive concepts can be configured to be positioned in one or moreintestinal and/or other locations of the patient, such as to perform afunction (e.g. perform a treatment, deliver fluid and/or record data) atone or more contiguous or discontiguous tissue locations. Target tissueto be treated (e.g. ablated) comprises a three dimensional volume oftissue, and can include a first portion, a treatment portion, whosetreatment has a therapeutic benefit to a patient; as well as a secondportion, a “safety-margin” portion, whose treatment has minimal or noadverse effects to the patient. “Non-target tissue” can be identified(e.g. prior to and/or during the medical procedure), wherein thenon-target tissue comprises tissue whose treatment by the treatmentassembly and/or treatment element should be reduced or avoided such asto reduce or prevent an undesired effect to the patient.

The target tissue treatment can cause one or more modifications of thetarget tissue such as a modification selected from the group consistingof: modification of cellular function; cell death; apoptosis; instantcell death; cell necrosis; denaturing of cells; removal of cells; andcombinations of one or more of these. In some embodiments, the targettissue treatment is configured to create scar tissue. Target tissue canbe selected such that after treatment the treated target tissue and/orthe tissue that replaces the target tissue functions differently thanthe pre-treated target tissue, such as to have a therapeutic benefit forthe patient. The modified and/or replacement tissue (singly orcollectively “treated tissue”) can exhibit different properties than thepre-treated target tissue, such as different properties that are used totreat a patient disease or disorder. The treated tissue can havedifferent secretions and/or quantities of secretions than thepre-treated target tissue, such as to treat diabetes,hypercholesterolemia and/or another patient disease or disorder. Thetreated tissue can have different absorptive properties than the targettissue, such as to treat diabetes, hypercholesterolemia and/or anotherpatient disease or disorder. The treated tissue can have a differentsurface topography than the target tissue, such as a modification of thetopography of the inner wall of the GI tract that includes a smoothingor flattening of its inner surface, such as a modification in which theluminal surface area of one or more segments of the GI tract is reducedafter treatment. The effect of the treatment (e.g. the effect on thetarget tissue) can occur acutely, such as within twenty-four hours, orafter longer periods of time, such as greater than twenty-four hours orgreater than one week.

Target tissue to be treated can comprise two or more discrete tissuesegments, such as two or more axial segments of the GI tract. Eachtissue segment can comprise a full (e.g. approximately 360°) or partialcircumferential segment of the tissue segment. Multiple tissue segmentscan be treated with the same or different functional elements (e.g.treatment elements), and they can be treated simultaneously or insequential steps (e.g. sequential energy delivery steps that deliverenergy to multiple delivery zones). Multiple tissue segments can betreated in the same or different clinical procedures (e.g. proceduresperformed on different days). In some embodiments, a series of tissuesegments comprising a series of axial segments of the GI tract aretreated in a single clinical procedure. The first and second tissuesegments can be directly adjacent, they can contain overlapping portionsof tissue, and there can be gaps between the segments. Dissimilaritiesin treatment elements can include type and/or amount of energy to bedelivered by an energy delivery based treatment element. Dissimilaritiesin target tissue treatments can include: target tissue area treated;target tissue volume treated; target tissue length treated; targettissue depth treated; target tissue circumferential portion treated;ablative fluid type, volume and/or temperature delivered to a reservoirsuch as a balloon; ablative fluid type, volume and/or temperaturedelivered directly to tissue; energy delivery type; energy delivery rateand/or amount; peak energy delivered; average temperature of targettissue achieved during target tissue treatment; maximum temperatureachieved during target tissue treatment; temperature profile of targettissue treatment; duration of target tissue treatment; surface areareduction achieved by target tissue treatment; and combinations of oneor more of these.

Target tissue can include tissue of the duodenum, such as tissueincluding substantially all or a portion of the mucosal layer of one ormore axial segments of the duodenum (e.g. including all or a portion ofthe plicae circulares), such as to treat diabetes, hypercholesterolemiaand/or another patient disease or disorder, such as while leaving theduodenum anatomically connected after treatment. Target tissue caninclude one or more portions of a tissue layer selected from the groupconsisting of: mucosa; mucosa through superficial submucosa; mucosathrough mid-submucosa; mucosa through deep-submucosa; and combinationsof one or more of these. Replacement tissue can comprise cells that havemigrated from one or more of: gastric mucosa; jejunal mucosa; anuntreated portion of the duodenum whose mucosal tissue functionsdifferently than the treated mucosal tissue functions prior totreatment; and combinations of one or more of these. Replacement tissuecan include one or more tissue types selected from the group consistingof: scar tissue; normal intestinal mucosa; gastric mucosa; andcombinations of one or more of these. In some embodiments, replacementtissue comprises tissue that has been delivered onto and/or into tissueby a catheter of the present inventive concepts. In some embodiments,target tissue includes a treatment portion comprising the mucosal layerof the duodenum, and a safety-margin portion comprising a near-full orpartial layer of the submucosal layer of the duodenum. In someembodiments, the target tissue comprises nearly the entire mucosal layerof the duodenum, and can include a portion of the pylorus contiguouswith the duodenal mucosa and/or a portion of the jejunum contiguous withthe duodenal mucosa. In some embodiments, the target tissue comprisesall or a portion of the duodenal mucosa distal to the ampulla of Vater(e.g. avoiding tissue within at least 0.5 cm, 1.0 cm or 1.5 cm from theampulla of Vater while including tissue within 5 cm, 10 cm or 15 cmdistal to the ampulla of Vater). In these embodiments, the target tissuecan comprise at least 10%, at least 15%, at least 25%, at least 30% orat least 50% of the duodenal mucosa distal to the ampulla of Vater.Alternatively or additionally, the target tissue can comprise no morethan 70% or no more than 90% of the duodenal mucosa distal to theampulla of Vater. In these embodiments, tissue proximal to and/orproximate the ampulla of Vater can comprise non-target tissue (i.e.tissue whose treatment is avoided or at least reduced).

In some embodiments, the target tissue comprises at least a portion ofduodenal mucosal tissue, and the systems, methods and devices of thepresent inventive concepts are configured to counteract duodenal mucosalchanges that cause an intestinal hormonal impairment leading to insulinresistance in patients. In these embodiments, the therapy provided canimprove the body's ability to process sugar and dramatically improveglycemic control for patients with insulin resistance and/or Type 2diabetes. In some embodiments, target tissue is treated to preventand/or reduce cognitive decline (e.g. Alzheimer's Disease), such as byimproving sugar metabolism in the brain, overcoming insulin resistancein the brain, reducing toxicity of beta amyloid, reducing oxidativestress, and/or reducing inflammation in the brain associated withneuronal death. In some embodiments, target tissue is treated to:prevent liver fibrosis and/or cirrhosis (e.g. non-alcoholic fatty liverdisease NAFLD or non-alcoholic steatohepatitis NASH); reduce liver fat;reduce oxidative stress; and/or reduce inflammation in the liverassociated with liver fibrosis and toxicity.

Hormones released from the intestinal mucosa play an important role inmodulating glucose homeostasis, and different axial segments of theintestinal mucosa release different hormones in the fasting andpost-prandial state, in order to modulate blood glucose in the fastingand post-prandial states, respectively. After a meal, the proximalintestinal mucosa senses the intestine for ingested glucose and releasesa collection of hormones in response to this signal. These hormonesinitiate the process of insulin release into the bloodstream after ameal, but they also induce some insulin resistance to prevent thereleased insulin from causing hypoglycemia before the body has a chanceto absorb the ingested glucose. One such hormone that plays a role inthis is GIP. Distal gut hormones (produced in the jejunum or a moredistal location), on the contrary, allow the release of more insulin butalso play a role in helping the body now become sensitive to itscirculating insulin. Teleologically, the explanation for this differencein the type of gut hormones produced by different segments of theintestine is that enough glucose will have been absorbed by the timenutrients reach the distal intestine to allow the insulin to begin tofunction to reduce blood glucose levels. Releasing different hormones atdifferent times (e.g. from different segments of the intestine) enablesthe body to absorb and process glucose in such a way as to avoidhypoglycemia (blood sugars that are too low) and hyperglycemia (bloodsugars that are too high). In this way, intestinal hormonal signaling isimportant for whole body glucose homeostasis in the fasting andpost-prandial states. The treatment can also lead to weight loss throughdecreased absorption of nutrients, increased sensation of satiety,altered food preferences, increased energy expenditure, and combinationsof one or more of these.

In patients with Type 2 Diabetes, a lifetime of exposure to fat andsugar can lead to intestinal changes that occur in regions with thehighest exposure to these nutrients, predominantly in the proximalintestine. These changes are characterized by an excess proximalintestinal mucosa's hormonal contribution to the fasting andpost-prandial glucose homeostasis. The net result of these intestinalchanges is to create a condition of insulin resistance and impairedglucose tolerance. Treatment of duodenal mucosal tissue with thesystems, devices and methods of the present inventive concepts can beperformed to alter the intestinal mucosal hormone production from theregion of treated tissue. The treated tissue can then have an alteredhormonal secretion pattern that affects blood glucose levels in thefasting and post-prandial states. The tissue treatment of the presentinventive concepts can be performed to effect duodenal mucosal tissuesecretion of GIP and/or GLP-1. The tissue treatment can lead to changesin the blood levels of GIP and/or GLP-1 (and other gut hormones) thatcan lead to changes in glucose homeostasis in the fasting and/orpost-prandial states. The treatment can lead to changes in insulinand/or glucagon secretion from the pancreas and/or insulin and/orglucagon levels in the bloodstream. The treatment can lead to changes inpancreatic beta cell function and/or health through direct hormonalconsequences of the treated duodenal tissue and/or indirectly throughimproved blood glucose levels. In some embodiments, the treatment of thepresent inventive concepts is configured to at least one of reduce ablood glucose level and/or reduce a lipoprotein level.

Treatment of intestinal tissue (e.g. duodenal mucosal tissue) can beperformed to treat a disease and/or disorder selected from the groupconsisting of: diabetes; pre-diabetes; impaired glucose tolerance;insulin resistance; obesity or otherwise being overweight; a metabolicdisorder and/or disease; and combinations of one or more of these. Insome embodiments, treatment of intestinal tissue (e.g. at least duodenalmucosal tissue) using the systems, devices and/or methods of the presentinventive concepts can be performed to treat one or more disease and/ordisorder selected from the group consisting of: Type 2 diabetes; Type 1diabetes; “Double diabetes”; gestational diabetes; hyperglycemia;pre-diabetes; impaired glucose tolerance; insulin resistance;non-alcoholic fatty liver disease (NAFLD); non-alcoholic steatohepatitis(NASH); obesity; obesity-related disorder; polycystic ovarian syndrome(PCOS); hypertriglyceridemia; hypercholesterolemia; psoriasis; GERD;coronary artery disease (e.g. as a secondary prevention); stroke; TIA;cognitive decline; dementia; Alzheimer's; neuropathy; diabeticnephropathy; retinopathy; heart disease; diabetic heart disease; heartfailure; diabetic heart failure; and combinations of one or more ofthese. A near full circumferential portion (e.g. approximately) 360° ofthe mucosal layer of one or more axial segments of GI tissue can betreated. In some embodiments, less than 360° of one or more axialsegments of tubular tissue is treated, such as one or morecircumferential portions less than 350°, or between 300° and 350°, suchas to prevent a full circumferential scar from being created at the oneor more axial segment locations.

Target tissue can be selected to treat two or more patient diseases ordisorders, such as two or more patient diseases or disorders asdescribed herein.

Target tissue can comprise tissue of the terminal ileum, such as totreat hypercholesterolemia and/or diabetes. In these embodiments, thetarget tissue can extend into the proximal ileum and/or the colon.

Target tissue can comprise gastric mucosal tissue, such as tissueregions that produce ghrelin and/or other appetite regulating hormones,such as to treat obesity and/or an appetite disorder.

Target tissue can comprise tissue selected from the group consisting of:large and/or flat colonic polyps; margin tissue remaining after apolypectomy; and combinations of one or more of these. These tissuelocations can be treated to treat residual cancer cells.

Target tissue can comprise at least a portion of the intestinal tractafflicted with inflammatory bowel disease, such that Crohn's diseaseand/or ulcerative colitis can be treated.

Target tissue can comprise GI tissue selected to treat Celiac diseaseand/or to improve intestinal barrier function.

The functional assemblies, functional elements, systems, devices andmethods of the present inventive concepts can be configured to avoidablating or otherwise adversely affecting certain tissue, termed“non-target tissue” herein. Depending on the location of tissue intendedfor treatment (i.e. target tissue), different non-target tissue can beapplicable. In certain embodiments, non-target tissue can comprisetissue selected from the group consisting of: gastrointestinaladventitia; duodenal adventitia; the tunica serosa; the tunicamuscularis; the outermost partial layer of the submucosa; ampulla ofVater (also known as the papilla); pancreas; bile duct; pylorus; andcombinations of one or more of these.

In some embodiments, two or more clinical procedures are performed inwhich one or more volumes of target tissue are treated in each clinicalprocedure, such as is described in applicant's co-pending U.S. patentapplication Ser. No. 14/673,565, entitled “Methods, Systems and Devicesfor Performing Multiple Treatments on a Patient”, filed Mar. 30, 2015.For example, a second clinical procedure can be performed at leasttwenty-four hours after the first clinical procedure, such as a secondclinical procedure performed within 6 months of a first clinicalprocedure or a clinical procedure performed after at least 6 monthsafter the first clinical procedure. The first and second clinicalprocedures can be performed using similar or dissimilar methods, andthey can be performed using similar or dissimilar systems and/or devices(e.g. performed with similar or dissimilar treatment and/or otherfunctional elements). The first and second clinical procedures can treatsimilar or dissimilar volumes of target tissue (e.g. similar ordissimilar amounts of tissue treated and/or locations of tissuetreated), and they can deliver energy to similar or dissimilar sets ofmultiple delivery zones. In some embodiments, the first and secondclinical procedures can include treating and/or delivering energy tocontiguous and/or overlapping regions of the GI tract either in thecircumferential and/or axial dimensions. In other embodiments, the firstand second clinical procedures can include the treatment of disparateregions of the GI tract (such as disparate regions of the duodenum,ileum, and/or stomach). The first and second clinical procedures can beperformed using similar or dissimilar devices (e.g. catheters). Thefirst and second clinical procedures can comprise similar or dissimilardeliveries of energy to treat the target tissue. The first and secondclinical procedures can be performed at similar or dissimilartemperatures. The second clinical procedure can be performed based ondiagnostic results collected after the first clinical procedure has beenperformed, such as when the diagnostic results are based on a biopsy ofmucosal tissue.

The functional assemblies, treatment assemblies, treatment elements andother functional elements of the present inventive concepts can comprisean expandable element or otherwise be configured to automatically and/ormanually expand or traverse in at least one radial direction. Typicalexpandable elements include but are not limited to: an inflatableballoon; a radially expandable cage or stent; one or more radiallydeployable arms; an expandable helix; an unfurlable compacted coiledstructure; an unfurlable sheet; an unfoldable compacted structure; andcombinations of one or more of these. In some embodiments, an expandableelement can comprise a radially expandable tube, such as a sheet ofmaterial resiliently biased in a radially expanded condition that can becompacted through a furling operation, or a sheet of materialresiliently biased in a radially compact condition that can be expandedthrough an unfurling operation. An expandable element can comprise afoldable sheet, such as a sheet configured to be folded to be radiallycompacted and/or to be unfolded to radially expand. In some embodiments,an expandable element expands to contact tissue, such as to expand to adiameter similar to the diameter of the luminal wall tissue into whichthe expandable element has been placed. In some embodiments, anexpandable element expands to be closer to wall tissue, but remain at adistance (e.g. a fixed or pre-determined distance) from the tissuesurface, such as when the tissue is subsequently brought into contactwith all or a portion of an expanded functional assembly or functionalelement (e.g. using insufflation fluid withdrawal techniques). In someembodiments, an expandable element expands to be larger than thediameter of the luminal wall tissue into which the expandable elementhas been placed, such as to improve the quality of the apposition of theexpandable element against the uneven surface of the tissue. In theseembodiments, the fully expanded diameter of an expandable element wouldbe configured to avoid a diameter large enough to cause lastingmechanical damage to the apposed tissue and/or to tissue proximate theapposed tissue. In some embodiments, the expansion of an expandableelement (e.g. the expansion of an expandable functional assembly) ismonitored and/or varied (e.g. decreased and/or increased), such as toaccommodate or otherwise compensate for peristalsis or other musclecontractions that occur in the GI tract (e.g. contractions that occurwhen a foreign body is present in the GI tract) and/or varied toaccommodate changes in GI lumen diameter imposed by aspects of theprocedure itself.

Any device (e.g. catheter) of the present inventive concepts can includeone or more functional elements comprising one or more treatmentelements configured to deliver energy to one or more delivery zones, totreat at least a portion of target tissue. Any device can include one ormore functional elements comprising one or more fluid delivery elements,such as one or more nozzles or needles configured to deliver fluidtoward and/or into tissue. The fluid delivery elements can beconstructed and arranged to deliver fluid to perform a function selectedfrom the group consisting of: expanding one or more tissue layers;warming or cooling tissue; removing debris or other substance from atissue surface; delivering energy to a delivery zone comprising acontinuous or segmented surface; treating target tissue; andcombinations of one or more of these. Any of the expandable functionalassemblies of the present inventive concepts can include one or moreother functional elements, such as are described herein. The treatmentelements and/or other functional elements (e.g. fluid delivery elements)can be mounted on, within (e.g. within the wall) and/or inside of anexpandable element such as a balloon or expandable cage. In someembodiments, one or more functional elements is not mounted to anexpandable element, such as those attached to a shaft or othernon-expandable catheter component.

In some embodiments, a catheter comprises at least one functionalelement configured to deliver energy to a delivery zone such as toablate target tissue. Examples of ablation-based functional elementsinclude but are not limited to: ablative fluids, such as hot or coldablative fluids delivered to a balloon and/or directly to target tissue;one or more fluid delivery elements configured to deliver ablative fluiddirectly to target tissue; an RF and/or microwave energy deliveryelement such as one or more electrodes; an ultrasonic and/or subsonictransducer such as one or more piezo crystals configured to ablatetissue with ultrasonic or subsonic energy, respectively, sound waves; alaser energy delivery element such as one or more optical fibers, laserdiodes, prisms and/or lenses; a rotating ablation element; acircumferential array of ablation elements; and combinations of one ormore of these.

The expandable elements comprising balloons of the present inventiveconcepts can be divided into two general categories: those that arecomposed of a substantially elastic material, such as silicone, latex,low-durometer polyurethane, and the like; and those that are composed ofa substantially inelastic material, such as polyethylene terephthalate(PET), nylon, high-durometer polyurethane and the like. A third categoryincludes balloons which include both elastic and inelastic portions.Within the category of elastic balloons, two subcategories exist: afirst sub-category wherein a combination of material properties and/orwall thickness can be combined to produce a balloon that exhibits ameasurable pressure-threshold for inflation (i.e. the balloon becomesinflated only after a minimum fluidic pressure is applied to theinterior of the balloon); and a second sub-category, wherein the balloonexpands elastically until an elastic limit is reached which effectivelyrestricts the balloon diameter to a maximum value. The individualproperties of the balloons in each of these categories can be applied toone or more advantages in the specific embodiments disclosed herein,these properties integrated singly or in combination. By way of exampleonly, one or more of the following configurations can be employed: ahighly elastic balloon can be used to achieve a wide range of operatingdiameters during treatment (e.g. during operation a desired balloondiameter can be achieved by adjustment of a combination of fluidtemperature and pressure); a substantially inelastic balloon or aballoon that reaches its elastic limit within a diameter approximating atarget tissue diameter (e.g. a duodenal mucosal diameter) can be used toachieve a relatively constant operating diameter that will besubstantially independent of operating pressure and temperature; aballoon with a pressure-threshold for inflation can be used to maintainan uninflated diameter during relatively low pressure conditions offluid flow and then achieve a larger operating diameter at higherpressure conditions of flow. Pressure-thresholded balloons can beconfigured in numerous ways. In one embodiment, a balloon is configuredto have a relatively thick wall in its uninflated state, such as tomaximize an electrically and/or thermally insulating effect while theballoon is maintained in this uninflated state. The balloon can befurther configured such that its wall thickness decreases during radialexpansion (e.g. to decrease an electrically and/or thermally insulatingeffect). In another embodiment, a balloon is configured to have arelatively small diameter in its uninflated state (e.g. a diameter thatis small relative to the inner diameter of tubular target tissue such asthe diameter of the mucosal layer of duodenal wall tissue), such as tominimize or completely eliminate apposition between the balloon and thesurrounding tissue to minimize heat, RF and/or other energy transferinto the surrounding tissue until the balloon is fully inflated. Inanother embodiment, a balloon and an ablation system or catheter areconfigured to circulate a flow of fluid through the balloon (e.g. anelastic balloon or an inelastic balloon) at a sufficiently low enoughpressure to prevent apposition of the balloon or other cathetercomponent with target tissue, such as to pre-heat one or more surfacesof the ablation system or ablation device that are in fluidcommunication with the balloon. In this configuration, when the balloonor other ablation element is positioned to deliver energy to targettissue, the temperature of the balloon or other ablation element will beat a desired level or it will rapidly and efficiently reach the desiredlevel for treatment (i.e. minimal heat loss to the fluid path componentsdue to the pre-heating or pre-cooling). These configurations provide amethod of delivering energy to tissue with an ablative fluid filledballoon. A “thermal priming” procedure can be performed prior to one ormore target tissue treatments, such as to improve thermal response timeof one or more portions of the catheter. Ablative fluid filled ballooncatheters as well as thermal priming devices and methods can beconfigured as is described in applicant's co-pending U.S. patentapplication Ser. No. 14/470,503, entitled “Heat Ablation Systems,Devices and Methods for the Treatment of Tissue”, filed Aug. 27, 2014,the content of which is incorporated herein by reference in its entiretyfor all purposes.

A fluid evacuation procedure can be performed on one or more internallocations of the catheters, functional assemblies and/or functionalelements of the present inventive concepts, such as when a negativepressure is applied to purge or otherwise evacuate fluid from one ormore locations. A fluid evacuation procedure can be performed prior to athermal priming procedure and/or prior to delivering ablative fluid to atreatment element.

At times during target tissue treatment when it is desirable toinitiate, increase and/or otherwise modify the treatment of tissue byone or more treatment elements (e.g. a fluid delivery element deliveringablative fluid, a mechanically abrasive element, a hot or cold fluidballoon delivering a thermal energy to tissue and/or an electrodedelivering RF energy), the diameter of the treatment assembly and/ortreatment element (e.g. the diameter of a balloon, deployable cage,expandable tube or other expandable assembly) can be increased in situto move a treatment element closer to target tissue and/or to change thecontact force between the treatment element and the target tissue. Attimes during treatment when it is desirable to stop or otherwisedecrease the amount of tissue treatment, the diameter of the treatmentassembly and/or treatment element can be reduced in situ, such as toprevent or otherwise reduce delivery of energy or other treatment to thetarget tissue by eliminating or reducing tissue contact of one or moretreatment elements (e.g. electrodes, abrasive surfaces or ablativefluid-filled balloons). For those cases where the native diameter of thetarget tissue varies substantially within a delivery zone, then a highlyelastic or compliant balloon or other expandable element can beemployed, such as a balloon or deployable cage which can be adjusted toachieve a wide range of operating diameters.

Alternatively or additionally, to initiate, increase and/or otherwisemodify the treatment of tissue by one or more functional elements (e.g.a fluid delivery element delivering ablative fluid, a mechanicallyabrasive element, a hot or cold fluid balloon delivering thermal energyto or from tissue and/or an electrode delivering RF energy), thediameter of the target tissue can be decreased in situ to move targettissue closer to a treatment element and/or to change the contact forcebetween the target tissue and the treatment element. To stop orotherwise decrease ablation of tissue, the diameter of tissueneighboring a treatment element can be increased in situ, such as toprevent or otherwise reduce delivery of energy or other treatment to thetarget tissue by eliminating or reducing tissue contact of one or moretreatment elements (e.g. electrodes, abrasive surfaces or ablative fluidfilled balloons). The diameter of the tissue proximate a functionalassembly can be increased or decreased, independent of the functionalassembly diameter, by means of delivering and/or withdrawing a fluid, toand/or from a body lumen (e.g. a lumen of a segment of the intestine)surrounded by target tissue, such as by using standard GI insufflationtechniques. Typical insufflation fluids include but are not limited to:gases such as carbon dioxide or air; liquids such as water or salinesolution; and combinations of one or more of these. The insufflationfluids can be introduced through a catheter, through an endoscope suchas an endoscope through which the catheter is inserted, and/or viaanother device placed proximate the target tissue. Delivery ofinsufflation fluids can be performed to move target tissue away from oneor more functional elements, such as to stop transfer of energy totarget tissue at the end of a treatment of target tissue as describedhereabove. Alternatively or additionally, delivery of insufflationfluids can be performed to manipulate tissue, such as to distend and/orelongate tissue. Extraction of these insufflation fluids and/or theapplication of a vacuum or other negative pressure can be used todecrease the diameter of the target tissue, such as to bring the targettissue in closer proximity to one or more functional elements and/or toincrease the contact force between target tissue and one or morefunctional elements, also as described hereabove. In this tissuediameter controlled approach, a functional assembly including a balloonthat can be maintained at a substantially constant diameter can bedesirable, such as a substantially inelastic balloon such as a balloonwith an elastic-limit.

The systems of the present inventive concepts can include one or moretissue expansion catheters that comprise one or more functional elementsconfigured as fluid delivery elements. In these embodiments, the one ormore functional elements can comprise one or more needles, nozzlesand/or fluid jets configured to deliver one or more fluids or otherinjectates to tissue, such as to expand target tissue and/or tissueproximate the target tissue (e.g. safety margin tissue) prior totreatment of target tissue by a tissue treatment element. The expandedtissue layer acts as a safety volume of tissue, reducing the specificityof the treatment (e.g. ablation) required and/or the need to protect theunderlying non-target tissue from damage. In some embodiments, a vacuumpressure can be used to manipulate tissue and/or to maintain proximitybetween a portion of a tissue expansion device and tissue. The vacuumcan be provided by one or more vacuum sources, such as via one or moreoperator adjustable vacuum sources.

Referring now to FIG. 1, a schematic view of a system and device forperforming a medical procedure on a patient is illustrated, consistentwith the present inventive concepts. The medical procedure can comprisea diagnostic procedure, a therapeutic procedure or a combined diagnosticand therapeutic procedure. System 10 comprises one or more catheters 100(e.g. a catheter, flexible probe, or other elongate device for insertioninto a patient, hereinafter “catheter”), and console 200 which operablyattaches to the one or more catheters 100 (e.g. two, three or morecatheters 100). Catheter 100 comprises an elongate shaft, shaft 110,comprising one or more shafts. In some embodiments, shaft 110 comprisesmultiple shafts in a spiraled configuration (e.g. helical configuration)such as is described herebelow in reference to FIG. 11. In someembodiments, shaft 110 comprises a non-circular cross section, such asthe non-circular cross section of shaft 110 described herebelow inreference to FIG. 32 (e.g. to “hug” a second device such as an endoscopesimultaneously inserted into the patient). In some embodiments, shaft110 comprises one or more of: a braided portion; a tapered portion; aninsertable stiffening mandrel; a variable stiffness portion; andcombinations of one or more of these, as described herebelow.

Catheter 100 comprises functional assembly 130, which can be configuredto radially expand and contract. Functional assembly 130 can bepositioned on a distal portion of catheter 100 (e.g. on the distal endor a distal portion of shaft 110). In some embodiments, functionalassembly 130 comprises a non-circular cross section, such as thenon-circular cross section of functional assembly 130 describedherebelow in reference to FIG. 33 (e.g. to “hug” a second device such asan endoscope simultaneously inserted into the patient). Functionalassembly 130 can comprise one or more tissue-contacting portions, asdescribed hereabove (e.g. side walls of functional assembly 130 thatcontact inner wall tissue of the intestine or other GI lumen).Functional assembly 130 can comprise a tissue-contacting surface area(e.g. when expanded) of between 500 mm² to 3500 mm², such as a tissuecontacting surface area of approximately between 1000 mm² and 2000 mm²,or approximately between 1250 mm² and 1750 mm², or approximately 1500mm². In some embodiments, functional assembly 130 comprises an expandeddiameter of approximately 19 mm, 22 mm, 25 mm or 28 mm. In someembodiments, functional assembly 130 comprises a tissue-contactinglength (e.g. when expanded) of between 10 mm and 40 mm, such as a lengthof approximately 15 mm, 20 mm, 25 mm or 30 mm. In some embodiments,system 10 includes a first catheter 100 comprising a functional assembly130 a with a first geometry, and a second catheter 100 comprising afunctional assembly 130 b with a second geometry different than thefirst geometry (e.g. a different length, expanded diameter; and/ortissue contacting surface area).

Catheter 100 can comprise one or more catheters of similar constructionand arrangement (e.g. and include similar components) as one or more ofdevices 100, 20, 30 and/or 40 of FIG. 2, each described in detailherebelow. Catheter 100 can be constructed and arranged to perform amedical procedure in an intestine of the patient, such as a procedure inthe small intestine (e.g. in the duodenum) and/or in the largeintestine. In some embodiments, system 10 further comprises connectingassembly 300 which can be constructed and arranged to operably attach(e.g. fluidly, mechanically, electrically and/or optically connect)catheter 100 to console 200. In alternate embodiments, catheter 100 canoperably attach directly to console 200, without connecting assembly300. Console 200 can be of similar construction and arrangement asconsole 200 of FIG. 2, also described in detail herebelow.

System 10 can further comprise body introduction device 50, one or moreguidewires 60, a sheath 80 (e.g. an endoscope-attachable sheath),injectate 221 and/or agent 420, each of which can be of similarconstruction and arrangement to the similar components described indetail herebelow in reference to FIG. 2. In some embodiments, guidewire60 comprises a guidewire of similar construction and arrangement to thatdescribed herebelow in reference to FIG. 26 or 26A. Body introductiondevice 50 can comprise an endoscope, a laparoscopic port and/or avascular introducer. Body introduction device 50 can comprise a camera,such as camera 52, and a display, not shown but such as a display ofconsole 200 and/or another display used to display an image (i.e. cameraview) provided by camera 52.

In some embodiments, system 10 further comprises imaging device 55,which can comprise an imaging device constructed and arranged to providean image of the patient's anatomy (e.g. inner wall or any part of theintestine of the patient) and/or an image of all or part of catheter 100or other portion of system 10, as described in detail herein. Imagingdevice 55 can comprise an imaging device selected from the groupconsisting of: endoscope camera; visible light camera; infrared camera;X-ray imager; fluoroscope; Ct Scanner; MRI; PET Scanner; ultrasoundimaging device; and combinations of one or more of these. In someembodiments, a patient image is used to set, confirm and/or adjust oneor more system 10 parameters, such as is described herebelow inreference to FIG. 41, such as when imaging device 55 comprises a sensorof the present inventive concepts configured to produce a signal.

In some embodiments, system 10 further comprises functional element 19comprising a sensor, transducer or other functional element. Functionalelement 19 can be operably attached to console 200 or another componentof system 10. Functional element 19 can comprise a sensor configured toproduce a signal, which can be used to modify a parameter of system 10,as described in detail herein. In some embodiments, functional element19 comprises a sensor configured to measure a patient parameter, such asa patient parameter selected from the group consisting of: a patientphysiologic parameter; blood pressure; heart rate; pulse distention;glucose level; blood glucose level; blood C-peptide level; bloodglucagon level; blood insulin level; blood gas level; hormone level;GLP-1 level; GIP level; EEG; LFP; respiration rate; breath distention;perspiration rate; temperature; gastric emptying rate; peristalticfrequency; peristaltic amplitude; a patient anatomical parameter such astissue geometry information; a patient environment parameter such asroom pressure or room temperature; and combinations of one or more ofthese.

In some embodiments, system 10 further comprises tool 500, such as atool 500 described herebelow.

In some embodiments, system 10 comprises one or more sensors, such aswhen one or more functional elements of system 10 are configured as asensor, such as functional elements 109, 119, 139, 229 and/or 309described in detail herebelow. Each of the system 10 sensors can beconfigured to produce a signal related to a patient parameter and/or asystem 10 parameter. For purposes herein, a signal “related” to aparameter shall include signals that directly represent the parameter,as well as signals that provide information that can be correlated to orin any way relate to the parameter. For example, a sensor (e.g. atemperature or pressure sensor) placed proximate tissue or a componentof system 10 can directly represent a parameter (e.g. the temperature orpressure, respectively) of or within that tissue or component.Alternatively, a sensor placed at one location (e.g. one location withinsystem 10), can provide a signal that can be analyzed to produceinformation representing a parameter at a different location (e.g. adifferent location within system 10 or a location within the patient).For example, a temperature or pressure measured at one location (e.g.within console 200, connecting assembly 300 and/or a proximal portion ofcatheter 100) can correlate to a temperature or pressure at a differentlocation (e.g. proximate and/or within functional assembly 130).Correlation of signals provided by a sensor of system 10 to a parameterat a location distant from the sensor can be accomplished by one or morealgorithms of system 10, such as algorithm 251 described herebelow.

In some embodiments, a system 10 sensor is configured to produce asignal related to an anatomic and/or physiologic parameter of thepatient, such as a parameter selected from the group consisting of: aparameter of the intestine; a parameter related to the anatomicalgeometry of a portion of the intestine; a parameter related to forceand/or pressure applied to tissue (e.g. tissue of the intestine); aparameter related to a pressure within tissue (e.g. tissue within theluminal surface of the intestine); a parameter related to temperature oftissue (e.g. tissue of the intestine); and combinations of one or moreof these. In some embodiments, one or more sensors of system 10 comprisea camera configured to provide an image, and the signal provided by thesensor comprises the image or an analysis of the image. The signalprovided by the sensor can relate to a patient parameter (e.g. a patientphysiologic or anatomical parameter) or a system 10 parameter (e.g. afunctional assembly 130 parameter).

In some embodiments, a system 10 sensor is configured to produce asignal related to a parameter of one or more components of system 10,such as a component of console 200, connecting assembly 300 and/orcatheter 100. For example, the signal produced by one or more sensors ofsystem 10 can be related to a functional assembly 130 parameter, such asa parameter selected from the group consisting of: pressure withinfunctional assembly 130; force applied to and/or by a portion offunctional assembly 130; temperature of at least a portion of functionalassembly 130; temperature of fluid within functional assembly 130; stateof expansion of functional assembly 130; position of functional assembly130 (e.g. position of functional assembly 130 relative to the patient'sanatomy): and combinations of one or more of these.

In some embodiments, system 10 is configured to perform a therapeuticprocedure selected from the group consisting of: a tissue removalprocedure such as a tissue removal procedure in which mucosal intestinaltissue is removed; a tissue ablation procedure such as a tissue ablationprocedure in which at least intestinal mucosal tissue is removed; atissue expansion procedure such as a tissue expansion procedureconfigured to create a safety margin of tissue and/or a tissue expansionprocedure configured to create a therapeutic restriction; andcombinations of one or more of these. In some embodiments, system 10 isconfigured to treat one or more patient diseases and/or disorders, suchas are described hereabove. For example, system 10 can be configured totreat diabetes, such as Type 2 diabetes, Type 1 diabetes, “Doublediabetes” and/or gestational diabetes. In some embodiments, system 10 isconfigured to treat hypercholesterolemia, such as when target tissuetreated by functional assembly 130 includes tissue of the terminalileum. In some embodiments, system 10 is configured to treat bothdiabetes and hypercholesterolemia. In some embodiments, system 10 isconfigured such that functional assembly 130 treats a part of theintestine exhibiting inflammatory bowel disease, ulcerative colitisand/or chronic ulcers. System 10 can be constructed and arranged tocause functional assembly 130 to expand one or more layers of tissue(e.g. submucosal tissue), and/or to treat target tissue (e.g. targettissue comprising mucosal tissue of the duodenum or other intestinalmucosa). System 10 can be further constructed and arranged to avoidadversely affecting non-target tissue, as described in detail herein andin applicant's co-pending application Ser. No. 13/945,138, entitled“Devices and Methods for the Treatment of Tissue”, filed Jul. 18, 2013,the content of which is incorporated herein by reference in its entiretyfor all purposes.

In some embodiments, system 10 is constructed and arranged to alterintestinal microbiota, such as to perform a treatment that affects apatient's gut flora in a way that leads to an improvement in weightand/or metabolic status (e.g. to treat Type 2 diabetes). Catheter 100and functional assembly 130 can be configured to treat target tissueincluding intestinal mucosa such as to destroy local bacteria and/ormodify the microbiome in the treated tissue area. Target tissue caninclude tissue regions where the microbiota contribute to the incidenceor maintenance of metabolic disease.

In some embodiments, system 10 is constructed and arranged to reduce orotherwise alter the surface area of intestinal mucosa, such as isdescribed in applicant's co-pending U.S. patent application Ser. No.14/956,710, entitled “Methods, Systems and Devices for Reducing theLuminal Surface Area of the Gastrointestinal Tract”, filed Dec. 2, 2015,the content of which is incorporated herein by reference in its entiretyfor all purposes. In some embodiments, system 10 is configured to reduceor otherwise alter the surface area of intestinal mucosa as a treatmentfor diabetes, a metabolic disease, obesity and/or hypercholesterolemia.In these embodiments, treatment of target tissue comprising mucosalfolds and/or other mucosal tissue results in intestinal mucosa withreduced plicae circulares and delayed recovery or regrowth of intestinalvilli. The treatment provided by system 10 can comprise a durabletreatment effect that reduces the total absorptive surface area of thetreated region. Alternatively or additionally, the treatment provided bysystem 10 can reduce enteroendocrine cell and/or absorptive cellquantities in the intestine by reducing the geometric complexity of theintestinal surface, such as by a target tissue treatment comprisingablation of intestinal tissue to a certain depth (mucosa alone; mucosaand superficial submucosa; mucosa through mid submucosa; or mucosathrough deep submucosa) that induces the healing response that leads toelimination of plicae circulares and blunting of villi for a prolongedperiod of time (at least 2 weeks, at least 6 weeks, at least 6 months orat least one year).

In some embodiments, system 10 is configured to treat sufficientduodenal mucosa to provide an improvement in a patient's diabetes, suchas is described in applicant's co-pending International PatentApplication Serial Number PCT/US2015/040775, entitled “Methods andSystems for Treating Diabetes and Related Diseases and Disorders”, filedJul. 16, 2015, the content of which is incorporated herein by referencein its entirety for all purposes.

In some embodiments, system 10 is configured to create a therapeuticrestriction in a patient, such as is described in applicant's co-pendingU.S. patent application Ser. No. 15/156,585, entitled “Systems, Devicesand Methods for the Creation of a Therapeutic Restriction in theGastrointestinal Tract”, filed May 17, 2016, the content of which isincorporated herein by reference in its entirety for all purposes. Insome embodiments, the therapeutic restriction is created at a locationselected from the group consisting of: within mucosal tissue; withinsubmucosal tissue; between mucosal and submucosal tissue; andcombinations thereof. In some embodiments, the therapeutic restrictionis created at a location selected from the group consisting of: lowerstomach; pylorus; proximal small intestine; duodenum; proximal jejunum;distal small intestine; distal jejunum; ileum; and combinations thereof.In some embodiments, the therapeutic restriction is created in alocation selected from the group consisting of: colon; rectum; analsphincter and combinations thereof. In some embodiments, the therapeuticrestriction is created by injecting (e.g. via one or more fluid deliveryelements 139 c) a volume of injectate 221 of at least 1.0 mL. Thetherapeutic restriction can be created by injecting a volume ofinjectate 221 of at least 3.0 mL, or at least 4.0 mL. In someembodiments, the therapeutic restriction is created by injecting avolume of injectate 221 of no more than 20.0 mL. The therapeuticrestriction can be created by injecting a volume of injectate 221 of nomore than 10.0 mL, or no more than 8.0 mL. In some embodiments, thetherapeutic restriction comprises an axial length between 1 mm and 100mm. The therapeutic restriction can comprise an axial length between 1mm and 20 mm. In some embodiments, the therapeutic restriction comprisesan inner diameter (e g diameter of its open portion) that is less thanor equal to 10 mm. The therapeutic restriction can comprise an innerdiameter less than or equal to 5 mm, 4 mm, 3 mm, 2 mm or 1 mm. In someembodiments, the therapeutic restriction comprises an inner diameterthat is between 1% and 50% (e.g. 99% to 50% narrowing, respectively) ofthe inner diameter of the luminal segment prior to creation of thetherapeutic restriction. The therapeutic restriction can comprise aninner diameter that is between 1% and 20% of the inner diameter of theluminal segment prior to creation of the therapeutic restriction. Theinner diameter of the therapeutic restriction can increase over time,such as via the therapeutic restriction volume decreasing over time suchas via absorption, migration or other reduction of the deliveredinjectate 221. The inner diameter of the therapeutic restriction canincrease to an inner diameter that is between 11% and 20% of the innerdiameter of the luminal segment prior to creation of the therapeuticrestriction. The therapeutic restriction can comprise an inner diameterthat is between 1% and 10% of the inner diameter of the luminal segmentprior to creation of the therapeutic restriction. The therapeuticrestriction can comprise an inner diameter that is between 1% and 5% ofthe inner diameter of the luminal segment prior to creation of thetherapeutic restriction.

System 10 can be constructed and arranged to perform one or morediagnostic procedures. In some embodiments, system 10 is constructed andarranged to perform a lumen sizing procedure, such as a procedure inwhich one or more diameters of one or more lumen locations in theintestine are determined (e.g. estimated). In these embodiments, therelative location at which the diameter is determined can be maintainedat a pressure at or near room pressure (e.g. via one or more lumens ofcatheter 100 and/or body introduction device 50. System 10 can beconstructed and arranged to perform a patient imaging procedure, such asa procedure in which a patient image is collected, such as a patientimage that includes functional assembly 130 positioned in a segment ofthe intestine. System 10 can be constructed and arranged to perform atissue sampling procedure, such as in a biopsy procedure. In someembodiments, system 10 is constructed and arranged to perform adiagnostic and/or other procedure selected from the group consisting of:assessment of mucosal thickness and/or hypertrophy, such as while usingOCT or similar imaging technologies; assessment of wall thickness, suchas via endoscopic ultrasound or similar imaging technologies;visualization of enteroendocrine cell populations, such as via molecularimaging techniques or antibody labeling; assessment of the location ofthe ampulla of Vater, such as via bile acid labeling; and combinationsof one or more of these. In some embodiments, system 10 is constructedand arranged to perform a therapeutic and/or other procedure selectedfrom the group consisting of: an obesity treatment procedure, such as anendoluminal implant of a balloon or other volume reducing and/orrestricting device in the stomach or small intestine, a suturing oranastomosing procedure to reduce and/or restrict gastrointestinalvolume, and/or an intestinal bypass; a procedure including the injectionof sclerosing material configured to induce scar formation; a procedureincluding the injection of material to create a therapeutic restriction;a procedure including the injection of drugs or other agents into thesubmucosal space; a microbial transplantation procedure, such as toalter gut microbial populations; and combinations of one or more ofthese.

In some embodiments, system 10 is constructed and arranged to perform apatient assessment, such as a patient screening to determine if anintestinal tissue ablation (e.g. a duodenal mucosa ablation) wouldbenefit the patient. In these embodiments, system 10 and/or the methodsof the present inventive concepts can be configured to compare glucagonadministered orally (PO) versus glucagon administered intravenously(IV). Data gathered can include the difference in the patient's abilityto suppress glucagon after a meal. Patient's whose ability to suppressglucagon falls below a threshold can be selected to receive a treatmentof the present inventive concepts (e.g. an ablation or other treatmentto at least the duodenal mucosa). Alternatively or additionally,analysis of fasting and/or postprandial glucagon can be compared to athreshold, and patients whose level is above the threshold can beselected to receive a treatment of the present inventive concepts (e.g.a treatment to at least the duodenal mucosa).

Catheter 100 of system 10 includes shaft 110, typically a flexible shaftcomprising one or more lumens. In some embodiments, shaft 110 comprisesvaried flexibility along its length, such as is described herebelow inreference to FIG. 27. Positioned on the distal end of catheter 100 isbulbous tip 115. Bulbous tip 115 can comprise a diameter of at least 4mm and/or a diameter less than or equal to 15 mm. In some embodiments,bulbous tip 115 comprises an inflatable bulbous tip as describedherebelow in reference to FIG. 5B. An operator graspable handle, handle102 is positioned on the proximal end of shaft 110. Handle 102 cancomprise a user interface 105, such as user interface 105 shown. Userinterface 105 can comprise one or more user input components and/or useroutput components. User interface 105 can comprise one or more userinput components configured to allow an operator to modify one or moreconsole settings 201, such as an operator-based modification based oninformation provided via a signal produced by a sensor of system 10.User interface 105 can comprise a control (e.g. control 104 describedherebelow in reference to FIG. 2) or other user input component selectedfrom the group consisting of: switch; keyboard; membrane keypad; knob;lever; touchscreen; and combinations of one or more of these. Userinterface 105 can comprise a user output component selected from thegroup consisting of: light such as an LED; display; touchscreen; audiotransducer such as a buzzer or speaker; tactile transducer such as aneccentric rotational element; and combinations of one or more of these.

Catheter 100 further includes functional assembly 130, which can bepositioned on a distal portion 100 _(DP) of catheter 100 as shown.Functional assembly 130 can be constructed and arranged to perform apatient diagnosis and/or perform a patient treatment, such as adiagnosis or treatment performed on tissue of the intestine. In someembodiments, functional assembly 130 comprises an expandable assemblyconstructed and arranged to radially expand as determined by an operatorof system 10. Functional assembly 130 can comprise an expandable elementselected from the group consisting of: an inflatable balloon (e.g.balloon 136 as shown); a radially expandable cage or stent; one or moreradially deployable arms; an expandable helix; an unfurlable compactedcoiled structure; an unfurlable sheet; an unfoldable compactedstructure; and combinations of one or more of these. Functional assembly130 is shown in a radially expanded state in FIG. 1. Balloon 136 cancomprise a compliant balloon, a non-compliant balloon and/or a balloonwith compliant and non-compliant sections, as described hereabove.Balloon 136 can comprise a pressure-thresholded balloon, also asdescribed hereabove. Balloon 136 can comprise a multi-layerconstruction, such as a construction with different materials positionedin different layers of balloon 136. In some embodiments, at least thedistal portion of catheter 100, distal portion 100 _(DP), is constructedand arranged to be: inserted through an endoscope such as bodyintroduction device 50; inserted alongside an endoscope; inserted over aguidewire such as guidewire 60; inserted through a sheath such as scopeattachable sheath 80; inserted through an introducer such as sheath 90(e.g. an introducer sheath); and combinations of one or more of these.

Positioned within shaft 110 are one or more conduits or lumens, conduits111. Conduits 111 can comprise a conduit selected from the groupconsisting of: a fluid transport conduit (e.g. a tube or lumenconfigured to deliver fluids to functional assembly 130 and/or extractfluids from functional assembly 130); a tube comprising a lumen; a tubecomprising a translatable rod; a hydraulic tube; a pneumatic tube; atube configured to provide a vacuum (e.g. provide a vacuum to port 137);a lumen of shaft 110; an inflation lumen; a lumen configured to providea vacuum (e.g. provide a vacuum to port 137); a fluid delivery lumen; awire such as an electrically conductive wire; a linkage; a rod; aflexible filament; an optical fiber; and combinations of one or more ofthese. One or more conduits 111 can be configured to: transport fluid(e.g. deliver fluid and/or extract fluid); extract fluid; provide apositive pressure; provide a vacuum; and combinations of one or more ofthese. One or more conduits 111 can comprise a hollow tube, such as atube comprising polyimide and/or a tube comprising a braid, such as abraided polyimide tube. One or more conduits 111 can be configured toallow the transport of: power, signals and/or materials such as fluids.A conduit 111 can be configured to slidingly receive a guidewire (e.g.guidewire 60), such as for over-the-wire delivery of catheter 100, suchas when a conduit 111 is operably connected to guidewire lumen 116 ofbulbous tip 115. Alternatively, guidewire lumen 116 can both enter andexit bulbous tip 115 (as shown in FIG. 1), such as for rapid-exchangemanipulation of catheter 100 over a guidewire. In some embodiments, oneor more conduits 111 can be translated within shaft 110 (e.g. advancedand/or retracted), such as to change the position of a distal end of aconduit 111 (e.g. to change the position of an outflow tube or inflowtube within functional assembly 130).

Shaft 110 can comprise one or more functional elements, such asfunctional element 119 shown. Functional element 119 can be positionedon (e.g. on the outer surface of), in (e.g. within the wall of) and/orwithin (e.g. within a lumen of) shaft 110. Functional element 119 can bepositioned proximate (e.g. nearby, on, in and/or within) one or moreconduits 111, such as when functional element 119 comprises a valve,heating element and/or cooling element configured to exert a forceand/or alter the temperature of one or more fluids passing within aconduit 111.

Functional assembly 130 can comprise one or more functional elements139, such as treatment element 139 a, sensor 139 b and/or fluid deliveryelement 139 c. Each functional element 139 can comprise a sensor, atransducer and/or other functional element, as described in detailherein.

In some embodiments, one or more functional elements 139 are constructedand arranged as a tissue treatment element of the present inventiveconcepts, as described herein, such as when treatment element 139 acomprises an energy delivery element configured to treat target tissueof the intestine. Treatment element 139 a can be of similar constructionand arrangement as treatment element 135 described herebelow inreference to FIG. 2. Treatment element 139 a can comprise a treatmentelement selected from the group consisting of: an ablative fluid (e.g.an ablative fluid to be maintained within balloon 136 and/or an ablativefluid to be delivered onto tissue such as via a fluid delivery element139 c); an electrode configured to deliver radiofrequency (RF) or otherelectrical energy to tissue; an optical element (e.g. a lens or a prism)configured to deliver light energy to tissue; a sound energy deliveryelement such as a piezo crystal configured to deliver ultrasound orsubsonic sound energy to tissue; an agent delivery element such as aneedle, nozzle or other fluid delivery element configured to deliver anablative or other agent onto and/or into tissue; and combinations of oneor more of these. In some embodiments, treatment element 139 a comprisesfluid at an ablative temperature. In these embodiments, treatmentelement 139 a can comprise fluid whose temperature changes, such as whensystem 10 is configured to introduce a fluid both at an ablativetemperature and fluid at a neutralizing temperature, such as when fluidat a neutralizing temperature is delivered within functional assembly130 before and/or after fluid at an ablative temperature is deliveredwithin functional assembly 130, as described in detail herein.

In some embodiments, one or more functional elements 139 are constructedand arranged to perform a diagnosis, such as when sensor 139 b comprisesa sensor configured to sense a physiologic parameter of intestinaltissue. Sensor 139 b can comprise one or more sensors, such as aredescribed in detail herebelow.

In some embodiments, one or more functional elements 139 are constructedand arranged to expand tissue, such as when fluid delivery element 139 ccomprises one or more of: a needle, nozzle, fluid jet, iontophoreticfluid delivery element, an opening in functional assembly 130 (e.g. anopening in balloon 136) and/or other fluid delivery element configuredto deliver fluid into and/or onto tissue. In some embodiments, fluiddelivery element 139 c comprises an element (e.g. a needle or fluid jet)configured to deliver fluid into tissue, such as submucosal tissue, toexpand the tissue receiving the injected fluid. Alternatively oradditionally, fluid delivery element 139 c can comprise an element (e.g.a nozzle) configured to deliver fluid onto tissue, such as ablativefluid delivered onto tissue to ablate and/or remove tissue orneutralizing fluid configured to reduce tissue trauma. Fluid deliveryelement 139 c can comprise a needle selected from the group consistingof: a straight needle; a curved needle; a single lumen needle; amultiple lumen needle; and combinations of one or more of these. In someembodiments, one or more fluid delivery elements 139 c comprise atissue-engaging fluid delivery element, such as is described herebelowin reference to FIG. 30A or 30B. Fluid delivery element 139 c can bepositioned proximate and/or within a port, such as port 137 shown. Port137 can be placed on top of balloon 136 and/or recessed into balloon 136(e.g. positioned within a recess of balloon 136 or other component offunctional assembly 130). Port 137 can be engaged between layers ofballoon 136, such as when balloon 136 comprises multiple layersincluding an outer layer (e.g. a layer of PET) that surrounds at least aportion of port 137. In some embodiments, port 137 comprises aninsulating element, such as an insulating element configured to preventfull circumferential ablation of an axial segment of intestine, asdescribed herebelow in reference to FIG. 20. Port 137 can be positionedon a tissue-contacting portion of balloon 136 as shown. Port 137 can beattached to a source of vacuum, such as vacuum provided by a conduit111, such that port 137 can engage with the tissue. Port 137 can beconstructed and arranged such that tissue can be drawn into port 137,such as when tissue is drawn into port 137 prior to delivery of fluid byfluid delivery element 139 c into tissue, as described herein. In someembodiments, catheter 100 comprises multiple ports 137 and multiplecorresponding fluid delivery elements 139 c, such as two, three or morepairs of ports 137 and fluid delivery elements 139 c (e.g. equallyspaced about a circumference of balloon 136). One or more functionalelements 139 can be attached to one or more conduits 111 and can beconfigured to be translated (e.g. translated within a port 137).Translation of a fluid delivery element 139 c can be limited by one ormore mechanical stops constructed and arranged to limit advancementand/or retraction of fluid delivery element 139 c. One or more fluiddelivery elements 139 c and a fluidly attached conduit 111 can be biasedby one or more springs, such as one or more springs positioned in handle102. Fluid delivery element 139 c and an associated functional assembly130 can be of similar construction and arrangement as those describedherebelow in reference to catheter 20 and/or catheter 40 of FIG. 2, oras described in applicant's co-pending application Serial NumberPCT/US2015/022293, entitled “Injectate Delivery Devices, Systems andMethods”, filed Mar. 24, 2015, the content of which is incorporatedherein by reference in its entirety for all purposes. One or more fluiddelivery element 139 c can comprise a straight or a curved needle. Oneor more fluid delivery elements 139 c can be constructed and arranged toenter tissue at an angle between 0° and 90°, such as at an angle between30° and 60°.

Functional assembly 130 can be configured to treat target tissue, suchas when functional element 139 comprises ablative fluid introduced intoballoon 136 or when functional element 139 comprises one or more energydelivery elements as described herein. Functional assembly 130 can beconstructed and arranged to treat a full or partial circumferentialaxial segment of intestinal tissue (e.g. intestinal mucosa). System 10can be configured to treat multiple axial segments of tissue, such asmultiple relatively contiguous or discontiguous segments of mucosaltissue treated simultaneously and/or sequentially. The multiple segmentscan comprise overlapping and/or non-overlapping borders.

Catheter 100 is configured to operably attach to console 200. In someembodiments, catheter 100 attaches directly to console 200. In otherembodiments, attachment assembly 300 is positioned and operably attachedbetween catheter 100 and console 200, such as to transfer materials(such as injectate 221, agent 420, hydraulic and/or pneumatic fluid,ablative fluids and/or other fluids), energy (such as ablative fluidsand/or electromagnetic energy), and/or data between catheter 100 andconsole 200. Attachment assembly 300 comprises end 301 which attaches tocatheter 100 via port 103 of handle 102. Attachment assembly 300 furthercomprises end 302 which attaches to console 200 via port 203 of console200. Conduits 311 of attachment assembly 300 operably attach conduits111 of catheter 100 to conduits 211 of console 200. Attachment assembly300 can comprise a cassette configuration configured to operably attachto console 200. Attachment assembly 300 can comprise one or moreflexible portions (e.g. coiled tubes and/or filaments) that allowmovement of catheter 100 relative to console 200, such as to extendcatheter 100 away from console 200 and toward a table onto which apatient is positioned. Attachment assembly 300 can comprise one or morefunctional elements 309, such as an array of functional elements 309,each positioned proximate a conduit 311. Each functional elements 309can comprise a sensor, transducer and/or other functional element asdescribed in detail herein.

Console 200 is configured to operably control and/or otherwise interfacewith catheter 100. In some embodiments, console 200 comprises one ormore pumping assemblies 225 (four shown in FIG. 1), which can each beattached to a reservoir 220 via one or more conduits 212. Each reservoir220 can be constructed and arranged to store and supply fluids tocatheter 100 and/or to extract fluids from catheter 100, such as isdescribed herebelow in reference to system 10 of FIG. 2. An ablativefluid, a neutralizing fluid, agent 420 and/or injectate 221 can beplaced or otherwise positioned within one or more reservoirs 220, suchas to be transported by one or more pumping assemblies 225 into one ormore conduits 111 of catheter 100 (e.g. via conduits 211 of console 200and optionally via conduits 311 of connecting assembly 300). In someembodiments, console 200 is constructed and arranged to deliver aneutralizing fluid (e.g. a cooling fluid or warming fluid containedwithin a reservoir 220), then an ablative fluid (e.g. a hot fluid and/ora cryogenic fluid, respectively, contained within one or more reservoirs220). In these embodiments, console 200 can be further constructed andarranged to subsequently deliver (i.e. after the ablation step), thesame or a different neutralizing fluid (e.g. a cooling fluid containedwithin a reservoir 200). In some embodiments, a first reservoir 220provides an ablative fluid comprising a hot fluid at a temperature above44° C., such as above 65° C., above 75° C., above 85° C. or above 95°C., and a second reservoir 220 provides a neutralizing fluid comprisinga cooling fluid below 37° C., such as below 20° C. or below 15° C. Insome embodiments, a first reservoir 220 provides an ablative fluidcomprising a cryogenic fluid, and a second reservoir 220 provides aneutralizing fluid comprising a warming fluid at or above 37° C.

Alternatively or additionally, console 200 can be configured to provideRF and/or light energy to functional assembly 130 to ablate or otherwisetreat tissue, and a cooling step can be performed (e.g. via aneutralizing fluid provided by a reservoir 220 comprising fluid below37° C.) prior to and/or after the delivery of the RF and/or lightenergy. In some embodiments, system 10 comprises two return paths, onefor recovery of ablative fluid (e.g. hot fluid), and one for recovery ofneutralizing fluid (e.g. cooling fluid), such as via separate conduits111, 311 and/or 211. In these embodiments, two separate pumpingassemblies 225 can be fluidly attached to the separate return paths.

Console 200 comprises one or more console settings 201 that can bevaried, such as a change made manually (e.g. by a clinician or otheroperator of system 10), and/or automatically by system 10. Controller250 can comprise one or more signal processors, such as signal processor252 shown. Signal processor 252 can be configured to analyze one or moresensor signals, such as to modify one or more settings 201 of console200. Controller 250 and/or signal processor 252 can comprise algorithm251 which can be configured to perform one or more mathematical or otherfunctions, such as to compare one or more sensor signals (e.g. comparethe signal itself or a mathematical derivation of the signal) to athreshold. Console settings 201 can comprise one or more parameters(e.g. system parameters as also referred to herein) of catheter 100,console 200 and/or any component of system 10. Console settings 201 cancomprise one or more parameters selected from the group consisting of:delivery rate of fluid into functional assembly 130; withdrawal rate offluid from functional assembly 130; delivery rate of fluid into tissue;rate of energy delivered into tissue; peak energy level delivered intotissue; average energy delivery rate delivered into tissue; amount ofenergy delivered into tissue during a time period; temperature of anablative fluid (e.g. temperature of an ablative fluid in reservoir 220,console 200, functional assembly 130 and/or catheter 100); temperatureof a neutralizing fluid (e.g. temperature of a neutralizing fluid inreservoir 220, console 200, functional assembly 130 and/or catheter100); temperature of functional assembly 130; pressure of functionalassembly 130; pressure of fluid delivered into functional assembly 130;pressure of fluid delivered into tissue; duration of energy delivery;time of energy delivery (e.g. time of day of or relative time comparedto another step); translation rate such as translation rate of afunctional assembly 130; rotation rate such as rotation rate of afunctional assembly 130; a flow rate; a recirculation rate; a heatingrate or temperature; a cooling rate or temperature; a sampling rate(e.g. a sampling rate of a sensor); and combinations of one or more ofthese. In some embodiments, one or more console settings 201 comprise asetting related to a system 10 parameter selected from the groupconsisting of: pressure and/or volume of a fluid delivered to shaft 110to change the stiffness of shaft 110 (e.g. to modify pushability and/ortrackability); pressure and/or volume of a fluid delivered to and/orextracted from functional assembly 130 for inflation and/or deflation(e.g. to obtain apposition of ports 137 and/or to anchor functionalassembly 130 in the intestine); pressure and/or volume of a fluiddelivered to one or more conduits 111, each configured as a fluidtransport tube to provide injectate 221 to one or more fluid deliveryelements 139 c (described herebelow) such as to advance and/or retractone or more fluid delivery elements 139 c and/or to deliver injectate221 into tissue (e.g. submucosal tissue); pressure and/or volume of afluid within one or more conduits 111, each configured to provide avacuum to one or more ports 137 to engage the one or more ports 137 withtissue and/or to cause a fluid delivery element to engage (e.g.penetrate) tissue; a force used to advance and/or retract one or moreconduits 111 and/or one or more fluid delivery elements 139 c; andcombinations of one or more of these. In some embodiments, one or moreconsole settings 201 comprise a setting related to a system 10 parameterselected from the group consisting of: temperature, flow rate, pressureand/or duration of fluid delivered to catheter 100 and/or functionalassembly 130; temperature, flow rate, pressure and/or duration of fluidcontained within functional assembly 130 and/or circulating loops (e.g.conduits 111, 211 and/or 311) of system 10: and combinations of one ormore of these. System 10 can be configured to adjust one or more consolesettings 201 based on one or more signals produced by one or moresensors of system 10. Based on the one or more sensor signals, system 10can be configured to modify a console setting 201 to cause: stoppingdelivery of fluid and/or energy to and/or by functional assembly 130;delivering additional fluid into functional assembly 130 and/or intotissue (e.g. adjust fluid delivery rate); delivering neutralizing and/orother additional fluid into functional assembly 130 and/or into tissue;adjusting the pressure of functional assembly 130; adjusting the volumeof functional assembly 130; and combinations of one or more of these. Insome embodiments, algorithm 251 is configured to determine an injectatedelivery parameter, such as the amount (e.g. volume and/or mass) ofinjectate 221 to be delivered by catheter 100.

In some embodiments, system 10 adjusts a functional assembly 130parameter based on a signal of a sensor of system 10. In theseembodiments, a functional assembly 130 parameter can be adjusted duringperformance of a procedural step, such as an ablation step or a tissueexpansion step. The functional assembly 130 parameter adjusted cancomprise a parameter selected from the group consisting of: volume offunctional assembly 130; diameter of functional assembly 130; pressureof functional assembly 130; force applied to tissue by functionalassembly 130; and combinations of one or more of these. The functionalassembly 130 parameter can be adjusted to prevent excessive force beingapplied to the intestinal wall or to maintain a minimum apposition levelof functional assembly 130 with tissue of the intestine.

In some embodiments, console 200 comprises a first reservoir 220containing hot fluid for ablation, a second reservoir 220 comprisingcooling fluid at a first temperature (e.g. a temperature less than 37°C. but more than 10° C.), and a third reservoir 220 comprising fluid ata second temperature cooler than the first temperature (e.g. atemperature less than 6° C., such as a temperature between 2° C. and 4°C.). Fluid from the third reservoir 220 can be delivered into the secondreservoir 220 (e.g. after one or more steps including cooling andablation of tissue have been performed).

In some embodiments, console 200 comprises a first reservoir 220containing hot fluid for ablation at a first temperature (e.g.approximately 55° C.), and a second reservoir 220 comprising hot fluidfor ablation at a second temperature (e.g. approximately 95° C.). Fluidfrom the first reservoir 220 and the second reservoir 220 can bedelivered to functional assembly 130 for equal time periods. In theseembodiments, console 200 can further comprise a third reservoir 220comprising cooling fluid, such as when console 200 is configured todeliver hot fluid from the first reservoir 220, followed by hot fluidfrom the second reservoir 220, followed by cooling fluid from the thirdreservoir 220. Console 200 can be further configured to deliver thecooling fluid prior to the delivery of the hot fluid from the firstreservoir 220. In some embodiments, fluid from a reservoir 220 isdelivered for a time period determined based on the temperature of fluidin that reservoir and/or based on the temperature of fluid in a separatereservoir 220, as described herebelow. For example, the amount ofablative fluid delivered by a reservoir 220 containing hot fluid can beadjusted based on the temperature of cooling fluid in a differentreservoir 220.

In some embodiments, console 200 comprises two functional elements 209,a first functional element 209 comprising a heating element and a secondfunctional element 209 comprising a cooling element. In theseembodiments, connecting assembly 300 can comprise a tubeset configuredto be engaged with console 200 to allow the first functional element 209to transfer heat into fluid within connecting assembly 300 and thesecond functional element 209 to extract heat from (i.e. cool) fluidwithin connecting assembly 300. In these embodiments, system 10 canavoid the need for heated and/or cooled reservoirs 220, such as whenconsole 200 further comprises a disposable fluid supply fluidly attachedto connecting assembly 300. Connecting assembly 300 can comprise areusable tubing set. Connecting assembly 300 can comprise a tubing setcomprising multiple lumens (e.g. multiple tubes each with one or morelumens, or a single tube with multiple lumens), such as at least a firstlumen configured to deliver inflation fluid (e.g. deliver inflationfluid to functional assembly 130 to perform a tissue expansion procedureand/or a tissue sizing procedure), and at least two lumens configured todeliver a recirculating fluid (e.g. to recirculate ablative hot or coldfluid within functional assembly 130 during a tissue ablationprocedure).

Console 200 can comprise controller 250. Controller 250 can compriseuser interface 205 which can deliver commands to controller 250 andreceive information (e.g. to be displayed) from controller 250. In someembodiments, console 200 comprises energy delivery unit (EDU) 260, suchas an energy delivery unit configured to provide one or more of: thermalenergy such as heat energy or cryogenic energy; electromagnetic energysuch as radiofrequency (RF) energy; light energy such as light energyprovided by a laser; sound energy such as subsonic energy or ultrasonicenergy; chemical energy; and combinations of one or more of these. EDU260 can be of similar construction and arrangement as EDU 260 describedherebelow in reference to FIG. 2. Console 200 can further compriseconduits 211 which can be operably connected to catheter 100 (e.g.operably connected to one or more conduits 111 or other components ofcatheter 100). Conduits 211 can comprise one or more fluid transporttubes fluidly attached to pumping assemblies 225 and/or any filamentbundle operably attached to controller 250 and comprising one or morefilaments selected from the group consisting of: a tube comprising alumen; a tube comprising a translatable rod; a hydraulic tube; apneumatic tube; a tube configured to provide a vacuum (e.g. provide avacuum to port 137); a lumen of shaft 110; an inflation lumen; a fluiddelivery lumen; a wire such as an electrically conductive wire; alinkage; a rod; a flexible filament; an optical fiber; and combinationsof one or more of these. Controller 250 can be operably connected to oneor more of reservoirs 220, pumping assemblies 225 and/or user interface205 via bus 213. Bus 213 can comprise one or more wires, optical fibersor other conduits configured to provide power, transmit data and/orreceive data.

In some embodiments, console 200 is configured to operably expandfunctional assembly 130, such as with a liquid or gas provided by areservoir 220 and propelled by an associated pumping assembly 225. Insome embodiments, console 200 is configured to deliver fluid to tissuevia one or more fluid delivery elements 139 c, such as with a fluid(e.g. injectate 221) provided by a reservoir 220 and propelled by anassociated pumping assembly 225. In some embodiments, console 200 isconfigured to deliver ablative fluid to functional assembly 130, such asablative fluid provided by a reservoir 220 and propelled by anassociated pumping assembly 225. In these embodiments, ablative fluidcan be recirculated to and from functional assembly 130 by console 200.In some embodiments, console 200 is configured to deliver energy, suchas electromagnetic or other energy, to functional assembly 130, such asvia controller 250. Each of these embodiments is described in detailherebelow in reference to system 10 of FIG. 2.

One or more reservoirs 220 can each comprise one more functionalelements 229 a and/or one or more pumping assemblies 225 can eachcomprise one or functional elements 229 b. Each functional elements 229a and/or 229 b (singly or collectively functional element 229) cancomprise a sensor, a transducer or other functional element. In someembodiments, one or more functional elements 229 comprise a heatingelement or a chilling element configured to heat or chill fluid within areservoir 220 and/or a pumping assembly 225. Alternatively oradditionally, one or more functional elements 229 comprise a sensor,such as a temperature sensor, pressure sensor and/or a flow rate sensorconfigured to measure the temperature, pressure and/or flow rate,respectively, of fluid within a reservoir 220 and/or pumping assembly225.

In some embodiments, controller 250 comprises one or more algorithms,such as algorithm 251 configured to operatively adjust one or moreoperating parameters of console 200 and/or catheter 100 (generallyconsole settings 201), such as an algorithm that analyzes data providedby one or more sensors of system 10. Algorithm 251 can be configured tocorrelate a signal received by one or more sensors of system 10positioned at a first location, to a parameter of system 10 or thepatient at a second location distant from the first location (e.g. asecond location proximal or distal to the first location). For example,a measured temperature or pressure within console 200 (e.g. viafunctional element 229 a or 229 b), connecting assembly 300 (e.g. viafunctional element 309) or catheter 100 (e.g. via functional element119), can provide a signal related to a parameter at a remote location,such as a parameter of functional assembly 130 or the patient. Algorithm251 can be configured to analyze a signal received from a firstlocation, and produce parameter information correlating to a secondlocation.

In some embodiments, console 200 is constructed and arranged to operablyattach and control multiple catheters 100, such as two or more catheters100 of similar construction and arrangement to devices 100, 20, 30and/or 40 described herebelow in reference to FIG. 2.

In some embodiments, injectate 221 comprises a material selected fromthe group consisting of: water; saline; a gel; a hydrogel; a proteinhydrogel; a cross-linked hydrogel; a cross-linked polyalkyleneiminehydrogel; autologous fat; collagen; bovine collagen; human cadavericdermis; hyaluronic acid; calcium hydroxylapatite; polylactic acid;semi-permanent PMMA; dermal filler; gelatin; mesna (sodium2-sulfanylethanesulfonate); and combinations of one or more of these. Insome embodiments, injectate 221 comprises beads (e.g. pyrolyticcarbon-coated beads) suspended in a carrier (e.g. a water-based carriergel). In some embodiments, injectate 221 comprises a solid siliconeelastomer (e.g. heat-vulcanized polydimethylsiloxane) suspended in acarrier, such as a bio-excretable polyvinylpyrrolidone (PVP) carriergel. In some embodiments, injectate 221 has an adjustable degradationrate, such as an injectate 221 comprising one or more cross linkers incombination with polyalkyleneimines at specific concentrations thatresult in hydrogels with adjustable degradation properties. In someembodiments, injectate 221 and/or agent 420 comprises living cells, suchas living cells injected into the mucosa or submucosa of the intestineto provide a therapeutic benefit.

In some embodiments, injectate 221 comprises a visualizable and/orotherwise detectable (e.g. magnetic) material (e.g. in addition to oneor more materials of above) selected from the group consisting of: adye; a visible dye; indigo carmine; methylene blue; India ink; SPOT™dye; a visualizable media; radiopaque material; radiopaque powder;tantalum; tantalum powder; ultrasonically reflective material; magneticmaterial; ferrous material; and combinations of one or more of these.

In some embodiments, injectate 221 comprises a material selected fromthe group consisting of: a peptide polymer (e.g. a peptide polymerconfigured to stimulate fibroblasts to produce collagen); polylacticacid; polymethylmethacrylate (PMMA); a hydrogel; ethylene vinyl alcohol(EVOH); a material configured to polymerize EVOH; dimethyl sulfoxide(DMSO); saline; material harvested from a mammalian body; autologousmaterial; fat cells; collagen; autologous collagen; bovine collagen;porcine collagen; bioengineered human collagen; dermis; a dermal filler;hyaluronic acid; conjugated hyaluronic acid; calcium hydroxylapatite;fibroblasts; a sclerosant; an adhesive; cyanoacrylate; a pharmaceuticalagent; a visualizable material; a radiopaque material; a visible dye;ultrasonically reflective material; and combinations of one or more ofthese. As described herein, in some embodiments, a volume of injectate221 is delivered into tissue to create a therapeutic restriction (e.g. atherapeutic restriction with an axial length between 1 mm and 20 mm), asdescribed herein, or as is described in applicant's co-pending U.S.patent application Ser. No. 15/156,585, entitled “Systems, Devices andMethods for the Creation of a Therapeutic Restriction in theGastrointestinal Tract”, filed May 17, 2016, the content of which isincorporated herein by reference in its entirety for all purposes. Insome embodiments, a volume of injectate 221 is delivered into tissue tocreate a safety margin of tissue prior to an ablation procedure, as isdescribed herein.

In some embodiments, injectate 221 comprises a fluorescent-labeledmaterial or other biomarker configured to identify the presence of abiological substance, such as to identify diseased tissue and/or othertissue for treatment by functional assembly 130 (e.g. to identify targettissue). For example, injectate 221 can comprise a material configuredto be identified by imaging device 55 (e.g. identify a visualizablechange to injectate 221 that occurs after contacting one or morebiological substances). In these embodiments, imaging device 55 cancomprise a molecular imaging device, such as when imaging device 55comprises a molecular imaging probe and injectate 221 comprises anassociated molecular imaging contrast agent. In these embodiments,injectate 221 can be configured to identify diseased tissue and/or toidentify a particular level of one or more of pH, tissue oxygenation,blood flow, and the like. Injectate 221 can be configured to bedelivered onto the inner surface of intestinal or other tissue, and/orto be delivered into tissue (i.e. beneath the surface).

In some embodiments, agent 420 comprises a material selected from thegroup consisting of: anti-peristaltic agent, such as L-menthol (i.e. oilof peppermint); glucagon; buscopan; hycosine; somatostatin; a diabeticmedication; an analgesic agent; an opioid agent; a chemotherapeuticagent; a hormone; and combinations of one or more of these.

In some embodiments, agent 420 comprises cells delivered into theintestine, such as living cells delivered into intestinal mucosa orsubmucosa via a fluid delivery element 139 c.

System 10 comprises one or more sensors, transducers and/or otherfunctional elements, such as functional element 109, functional element119 and/or functional element 139 (e.g. 139 a, 139 b and/or 139 c) ofcatheter 100 and/or functional element 209 and/or functional element 229(e.g. 229 a and/or 229 b) of console 200. In some embodiments, system 10comprises connecting assembly 300 which can include one or morefunctional elements 309.

In some embodiments, one or more functional elements 109, 119, 139, 209,229 and/or 309 comprise a transducer selected from the group consistingof: an energy converting transducer; a heating element; a coolingelement such as a Peltier cooling element; a drug delivery element suchas an iontophoretic drug delivery element; a magnetic transducer; amagnetic field generator; a sound generator; an ultrasound wavegenerator such as a piezo crystal; a light producing element such as avisible and/or infrared light emitting diode; a motor; a pressuretransducer; a vibrational transducer; a solenoid; a fluid agitatingelement; and combinations of one or more of these.

In some embodiments, one or more functional elements 109, 119, 139, 209,229 and/or 309 comprise a visualizable element, such as an elementselected from the group consisting of: a radiopaque marker; anultrasonically visible marker; an infrared marker; a marker visualizableby a camera such as an endoscopic camera; a marker visualizable by anMRI, a chemical marker; and combinations of one or more of these.

In some embodiments, one or more of functional elements 109, 119, 139,209, 229 and/or 309 comprise a sensor configured to produce a signal,the sensor selected from the group consisting of: physiologic sensor;blood glucose sensor; blood gas sensor; blood sensor; respirationsensor; EKG sensor; EEG sensor; neuronal activity sensor; blood pressuresensor; flow sensor such as a flow rate sensor; volume sensor (e.g. avolume sensor used to detect a volume of injectate 221 not deliveredinto tissue); pressure sensor; force sensor; sound sensor such as anultrasound sensor; electromagnetic sensor such as an electromagneticfield sensor or an electrode; gas bubble detector such as an ultrasonicgas bubble detector; strain gauge; magnetic sensor; ultrasonic sensor;optical sensor such as a light sensor; chemical sensor; visual sensorsuch as a camera; temperature sensor such as a thermocouple, thermistor,resistance temperature detector or optical temperature sensor; impedancesensor such as a tissue impedance sensor; and combinations of one ormore of these. Each sensor can be configured to produce a signal thatdirectly correlates to or is otherwise related to a patient parameter ora system 10 parameter. One or more console settings 201 can be manuallyadjusted (e.g. by a clinician or other operator of system 10) and/orautomatically (e.g. by an algorithm of system 10) based on the sensorsignal.

In some embodiments, one or more of functional elements 109, 119, 139,209, 229 and/or 309 comprise a pressure sensor that produces a signalrelated to one or more of: pressure within functional assembly 130; thelevel of apposition of functional assembly 130 with the intestine; thediameter of the intestine proximate functional assembly 130; muscularcontraction of the intestine; pressure within a reservoir 220; pressurewithin connecting assembly 300; pressure within a lumen of shaft 110;and combinations of one or more of these. One or more console settings201 can be adjusted (e g manually or automatically) based on thepressure sensor signal. In some embodiments, a pressure sensor producesa signal related to the pressure within functional assembly 130, console200 delivers and/or extracts fluids to and/or from functional assembly130 via one or more conduits 111, and console 200 adjusts the volume offunctional assembly 130 to maintain pressure in functional assembly 130below a threshold.

In some embodiments, one or more of functional elements 109, 119, 139,209, 229 and/or 309 comprise a temperature sensor that produces a signalrelated to one or more of: temperature of fluid in console 200 (e.g. inone or reservoirs 220); temperature of elongate shaft 110; temperatureof fluid within elongate shaft 110; temperature of functional assembly130; temperature of fluid within functional assembly 130; temperature ofan ablative fluid; temperature of a neutralizing fluid; temperature oftissue proximate the functional assembly; temperature of target tissue;temperature of non-target tissue; and combinations of one or more ofthese. One or more console settings 201 can be adjusted (e g manually orautomatically) based on the temperature sensor signal.

In some embodiments, system 10 comprises a sensor (e.g. a functionalelement 109, 119, 139, 209, 229 and/or 309 comprising a sensor)configured to detect a parameter related to a level of treatment oftissue, such as a parameter selected from the group consisting of:color, density and/or saturation of tissue (e.g. a color change totissue that occurs during ablation or to an injectate 221 present in thetissue during ablation or other treatment); temperature of local tissueand/or temperature of other body tissue; texture, length and/or diameterof villi or other mucosal feature (e.g. as detected via a camera-basedsensor, such as when ablation causes a blunting and/or drooping of villior other intestinal tissue); electrical resistance, impedance and/orcapacitance of tissue (e.g. as altered by ablation of tissue); pressureand/or force of peristaltic contractions (e.g. as altered by ablation oftissue); compliance of tissue and/or the entire duodenum in radialand/or axial directions (e.g. as altered by ablation of tissue);chemical composition of film adhered to mucosal tissue (e.g. as alteredby ablation); types, quantities and/or locations of bacterial coloniespresent (e.g. as altered by ablation); and combinations of one or moreof these.

In some embodiments, system 10 comprises a sensor (e.g. a functionalelement 109, 119, 139, 209, 229 and/or 309 comprising a sensor)configured to detect a parameter related to a level of tissue expansion,such as a parameter selected from the group consisting of: color,density and/or saturation related to injected dye or particles whichalter tissue appearance (e.g. as determined via a camera-based sensor);temperature of tissue (e.g. that can be altered briefly due to deliveryof injectate 221 and/or inflammation response due to injectate 221delivery); texture, length and/or diameter of villi or mucosal features(e.g. as determined via a camera-based sensor) such as spacing betweenvilli or other intestinal tissue features that can change (e.g.increased spacing, disappearance or reduction of plicae, blebs ofinjectate 221 present) due to submucosal tissue expansion; electricalresistance, impedance and/or capacitance of tissue (e.g. as altered bydelivery of injectate 221); pressure and/or force of peristalticcontractions (e.g. as altered by delivery of injectate 221); complianceof tissue and/or the entire duodenum in radial and/or axial directions(e.g. as altered by injectate 221, such as to make tissue more compliantuntil the muscularis layer is contacted); chemical composition of filmadhered to mucosa (e.g. as altered by injectate 221, such as wheninjectate 221 creates a biologic response that is detectable); types,quantities and/or locations of bacterial colonies present; andcombinations of one or more of these.

In some embodiments, system 10 comprises a sensor (e.g. a functionalelement 109, 119, 139, 209, 229 and/or 309 comprising a sensor)configured to assess engagement of port 137 with tissue (e.g. todetermine if adequate engagement is present during a tissue expansion ortissue ablation step in which vacuum is applied to port 137 to engageport 137 with tissue). In some embodiments, a sensor is positioned todetect injectate in a conduit 111 of catheter 100 in which the vacuum isapplied. In these embodiments, detection of sufficient injectate cancorrelate to inadequate engagement with tissue. The detector cancomprise an optical sensor, and/or a window which is visualizable by anoperator (e.g. to see injectate that is recovered), such as when theinjectate comprises visible material.

In some embodiments, one or more functional elements 109, 119, 139, 209,229 and/or 309 comprises one or more temperature sensors that produces asignal related to a first temperature representing the temperature ofablative fluid delivered to functional assembly 130 and a secondtemperature related to the temperature of fluid extracted fromfunctional assembly 130. In these embodiments, system 10 can beconfigured to assess (e.g. via algorithm 251) the effect (e.g. quantity)of tissue treated (e.g. depth of tissue ablated), such as by analyzingthe first temperature and the second temperature (e.g. a comparison ofthe two). In some embodiments, the first and/or second temperature ismeasured by one or more sensors of connecting assembly 300 (e.g. two ormore functional elements 309 comprising thermistors or other temperaturesensors) and/or one or more sensors of catheter 100 (e.g. two or morefunctional elements 109, 119 and/or 139 comprising thermistors or othertemperature sensors).

In some embodiments, one or more of functional elements 109, 119, 139,209, 229 and/or 309 comprise a sensor configured to provide a signalrelated to lumen diameter information. In these embodiments, the sensorcan comprise a sensor selected from the group consisting of: pressuresensor; optical sensor; sound sensor; ultrasound sensor; strain gauge;electromagnetic sensor; an imaging device such as a camera; andcombinations of one or more of these. One or more console settings 201can be adjusted (e g manually or automatically) based on the lumendiameter information.

In some embodiments, one or more of functional elements 109, 119, 139,209, 229 and/or 309 comprise a sensor including an imaging deviceconfigured to provide a signal related to image information. The imagingdevice can comprise a device selected from the group consisting of:visible light camera; infrared camera; endoscope camera; MRI; CtScanner; X-ray camera; PET Scanner; ultrasound imaging device; andcombinations of one or more of these. In these embodiments, controller250 or another assembly of system 10 can comprise signal processor 252and/or algorithm 251, each of which can be configured to analyze theimage information provided by the imaging device. One or more consolesettings 201 can be adjusted (e.g. manually or automatically) based onthe image information. Based on the image information, system 10 can beconfigured to modify a console setting 201 to cause an event selectedfrom the group consisting of: stopping delivery of fluid and/or energyto functional assembly 130; delivering additional fluid into functionalassembly 130 and/or into tissue; delivering neutralizing fluid intofunctional assembly 130 and/or into tissue; adjusting the pressure offunctional assembly 130; adjusting the volume of functional assembly130; and combinations of one or more of these.

In some embodiments, functional assembly 130 comprises a biasing member,such as biasing member 145 shown. Biasing member 145 is constructed andarranged to apply a force to functional assembly 130, such as to placefunctional assembly 130 in tension along the axis of shaft 110 proximatefunctional assembly 130, such as when functional assembly 130 is in anunexpanded state. Biasing member 145 can be constructed and arranged tobend as functional assembly 130 expands. Biasing member 145 can comprisean element selected from the group consisting of: spring; coil spring;leaf spring; flexible filament; flexible sheet; nickel titanium alloycomponent; and combinations of one or more of these. In someembodiments, functional assembly 130 comprises balloon 136, and biasingmember 145 is configured to avoid contacting balloon 136 when functionalassembly is in its unexpanded state.

In some embodiments, shaft 110 passes through all or a portion offunctional assembly 130. In other embodiments, functional assembly 130is positioned on a distal end of shaft 110.

In some embodiments, functional assembly 130 comprises a shapeconstructed and arranged to prevent or otherwise reduce migration offunctional assembly 130, such as is described herebelow in reference toFIG. 18. In some embodiments, functional assembly 130 is constructed andarranged to perform a first procedure (e.g. a tissue expansionprocedure), anchor in tissue (e.g. anchoring performed prior to thefirst procedure, during the first procedure and/or after the firstprocedure), and perform a second procedure (e.g. a tissue ablationprocedure), such as is described herebelow in reference to FIG. 35.

In some embodiments, functional assembly 130 and/or other components ofcatheter 100, connecting assembly 300 and/or console 200 are configuredto enhance mixing of one or more fluids within functional assembly 130(e.g. one or more functional element 139 comprising a fluid mixingelement). In some embodiments, one or more functional elements 139within functional assembly 130 comprise a baffle configured to improvefluid mixing and/or occupy a volume (e.g. a baffle positioned withinfunctional assembly 130). In some embodiments, one or more functionalelements 139 comprise an expandable and/or compressible baffle. Thesebaffles can be configured to “take up” volume within functional assembly130, such as to decrease the amount of fluid (e.g. ablative fluid)delivered into functional assembly 130 during a tissue ablation and/ortissue expansion procedure. The baffles can be configured to reduce risetimes or fall times of temperatures associated with functional assembly130 (e.g. reduce rise times or fall times to or from ablativetemperatures, respectively, during a tissue ablation procedure). Thebaffles can be configured to take up volume in between two or more ports137, such as to minimize the overall diameter of a catheter 100configured as a tissue expansion device.

In some embodiments, a first conduit 111 can comprise an inflow tubeconfigured to at least deliver fluid to functional assembly 130. Asecond conduit 111 can surround the first conduit 111, and an opening onthe proximal end of the second (outer) conduit 111 can be closed off(e.g. a proximal end of second conduit 111 positioned near the proximalend of functional assembly 130). The distal end of the second conduit111 can extend past the midpoint of functional assembly 130 butterminate proximal to the distal end of functional assembly 130, forminga collar around the inner first conduit 111 that channels the flow fromthe first conduit 111 to the distal portion of functional assembly 130,and improving mixing within all of the internal volume of functionalassembly 130.

In some embodiments, catheter 100 comprises one or more insulatingelements configured to avoid transfer of energy from shaft 110 totissue, such as an insulating element comprising a full or partial layerof shaft 110 that comprises thermally insulating material and/or aninsulating element comprising one or more conduits 111 which containcirculating fluid configured to dissipate heat from shaft 110.

Shaft 110 of catheter 100 can comprise one or more coatings 118, alongall or a portion of its outer and/or inner surfaces. In someembodiments, coating 118 is positioned on at least a portion of theouter surface of shaft 110, and is configured to prevent or otherwisereduce inadvertent translation of catheter 100 through the intestine(e.g. an anti-migration coating configured to reduce undesiredtranslation and/or rotation of catheter 100). Alternatively oradditionally (e.g. on a different portion), coating 118 can comprise alubricous coating. In some embodiments, coating 118 is positioned on oneor more lumens of shaft 110, such as a lubricous coating configured toassist in the translation of one or more filaments within the lumen. Insome embodiments, coating 118 comprises a coating positioned on at leasta portion of shaft 110 and selected from the group consisting of: ahydrophilic coating (e.g. to improve lubricity); a coating comprisingbumps (e.g. atraumatic projections configured to roughen a surface toreduce friction); a coating comprising a surface exposed to gritblasting (e.g. to roughen a surface to reduce friction); an insulativecoating: parylene; PTFE; PEEK; a coating comprising a colorant (e.g. toimprove or otherwise improve visibility of shaft 110 in-vivo); andcombinations of one or more of these. In some embodiments, coating 118comprises a coating positioned on at least a portion of functionalassembly 130 (e.g. on at least a portion of a balloon 136) and selectedfrom the group consisting of: a lubricous coating; a surface rougheningcoating; a silicone coating; an insulative coating; and combinations ofone or more of these.

In some embodiments, one or more functional elements 109, 119, 139, 209,229 and/or 309 comprise a filter (e.g. a hydrophobic filter) positionedin a fluid pathway of system 10. The filter can be positioned between asensor and the fluid pathway. In these embodiments, the associatedfunctional element 109, 119, 139, 209, 229 and/or 309 can furthercomprise a valve, such as a valve configured to vent the fluid pathwayproximate the filter.

In some embodiments, system 10 can be configured to deliver injectate221 to tissue to cause tissue expansion via a body fluid (e.g. viaosmotic pressure). For example, injectate 221 can comprise a saltsolution delivered by one or more fluid delivery elements 139 c thatcause water or other fluid to migrate from submucosal capillaries intothe submucosa.

In some embodiments, one or more of functional elements 109, 119, 139,209, 229 and/or 309 comprise a sensor configured to detect gas-bubbles,such as a gas bubble present in one or more of conduits 111, 211, 212and/or 311 and/or a gas bubble present in functional assembly 130. Insome embodiments, one or more de-gassing procedures are performed on oneor more components of system 10, and the one or more gas-bubble detectorbased functional elements 109, 119, 139, 209, 229 and/or 309 are used toconfirm that the de-gassing procedure is adequately completed and/or toindicate a de-gassing procedure should be performed.

In some embodiments, multiple conduits 111 are in fluid communicationwith functional assembly 130 (e.g. to simultaneously or sequentiallyinflate and/or deflate functional assembly 130) and/or port 137 (e.g. tosimultaneously or sequentially provide a vacuum to port 137). In theseembodiments, simultaneous and/or redundant delivery or extraction offluids (e.g. application of a vacuum) can be initiated based on thesignal provided by one or more sensors of system 10. For example, if asensor detects a first conduit 111 is fully or partially occluded, thesecond conduit 111 can be used to additionally or alternatively deliverand/or extract fluids.

In some embodiments, system 10 is configured to maintain the pressure offunctional assembly 130 relative to a threshold (e.g. pressure ismaintained below a pressure threshold, above a pressure threshold,and/or within a threshold comprising a range of pressures), such asduring treatment and/or diagnosis of target tissue of the intestine(e.g. during a tissue expansion and/or tissue ablation procedure).Functional assembly 130 can comprise a balloon 136 comprising acompliant balloon; a non-compliant balloon; a pressure-thresholdedballoon; and/or a balloon comprising compliant and non-compliantportions, as described herein. Pressure can be maintained at aparticular pressure or within a particular range of pressures bymonitoring one or more sensors of system 10, such as sensor 139 b and/ora sensor-based functional element 119, 109, 209 and/or 229. A lowerpressure threshold can comprise a pressure of 0.3 psi, 0.5 psi or 0.7psi. A lower pressure threshold can be selected to ensure sufficientcontact of functional assembly 130 with tissue. An upper pressurethreshold can comprise a pressure of 1.0 psi, 1.2 psi, 2.5 psi or 4.0psi. An upper pressure threshold can be selected to avoid damage totissue, such as damage to an outer layer of intestinal tissue (e.g. aserosal layer of the intestine). Pressure can be monitored such thatconsole 200 can modulate or otherwise control one or more inflow and/oroutflow rates of fluid delivered to and/or extracted from functionalassembly 130. Pressure can be monitored to maintain flow rates to orfrom functional assembly 130 to a minimum rate of at least 250 ml/min,500 ml/min, 700 ml/min or 750 ml/min. In some embodiments, pressure isdetermined by a sensor positioned outside of balloon 136, such as whenpressure is maintained in functional assembly within a narrow range ofpressures, such as at a pressure of between 1.05 psi and 0.55 psi. Inthese embodiments, a luminal sizing step can be avoided. In someembodiments, system 10 comprises one or more catheters 100 and/or one ormore functional assemblies 130, such as to provide an array offunctional assemblies 130 with different lengths and/or diameters. Inthese embodiments, the upper and/or lower pressure thresholds can beindependent of functional assembly 130 size.

In some embodiments, conduits 111 comprise an inflow tube and an outflowtube fluidly connected to functional assembly 130. Fluid can bedelivered to functional assembly 130 by console 200 via one or moreconduits 111 at various flow rates, such as flow rates up to 500 ml/min,1000 ml/min, 1500 ml/min, 2000 ml/min and/or 2500 ml/min Fluid can beextracted from functional assembly 130 by console 200 via one or moreconduits 111 at various flow rates, such as flow rates up to 500 ml/min,750 ml/min, or 1000 ml/min.

In some embodiments, treatment element 139 a can comprise fluid at asufficiently high temperature to ablate tissue (such as liquid above 60°C. or steam). Delivery of superheated fluid through a conduit 111 can beperformed, such as when functional element 119 comprises an orificeconfigured to cause the superheated fluid to boil upon enteringfunctional assembly 130, providing steam at 100° C. Delivery of cooledfluids through a conduit 111 can be performed. In some embodiments, afluid (cooled or otherwise) is introduced through a conduit 111 andthrough a functional element 119 comprising a valve, such that expansionof the fluid into functional assembly 130 results in a cooling effect.

In some embodiments, system 10 and catheter 100 are constructed andarranged to fill functional assembly 130 with neutralizing (e.g.chilled) fluid, and then thermally prime a first conduit 111 withablative (e.g. hot) fluid, when the first conduit is positioned in aretracted state (e.g. preventing or otherwise reducing heating offunctional assembly 130). Subsequently, the first conduit 111 isadvanced (i.e. first conduit 111 is constructed and arranged as atranslatable conduit) and ablative fluid is introduced into functionalassembly 130, allowing functional assembly 130 to be in a fully orpartially expanded state prior to fluid at an ablative temperatureresiding in functional assembly 130 and avoiding undesired “partialablative contact” of functional assembly 130 with tissue. Anotheradvantage of this configuration is that functional assembly 130 can bechecked for leaks with non-ablative fluid prior to one or moresubsequent steps (e.g. each ablation step).

In some embodiments, functional assembly 130 is constructed and arrangedto both expand tissue (e.g. expand submucosal tissue) and treat targettissue (e.g. treat duodenal mucosal tissue), such as is describedherebelow in reference to multi-function catheter 40 of FIG. 2. Forexample, functional assembly 130 can comprise fluid delivery element 139c which can be positioned to deliver fluid into tissue that has beendrawn into (e.g. upon application of a vacuum) port 137, to expand oneor more layers of tissue (e.g. one or more layers of submucosal tissue).Functional assembly 130 can further comprise treatment element 139 awhich can comprise ablative fluid which can be introduced intofunctional assembly 130 and/or an energy delivery element configured todeliver energy to tissue (e.g. RF energy, light energy, sound energy,chemical energy, thermal energy and/or electromagnetic energy), eachconfigured to perform a therapeutic treatment on target tissue.

In some embodiments, system 10 and catheter 100 are configured to bothexpand tissue (e.g. expand submucosal tissue of the intestine) and treattarget tissue (e.g. treat mucosal tissue of the intestine proximate theexpanded submucosal tissue). Catheter 100 can comprise a single catheter100 comprising one or more functional elements 139 configured tocollectively expand tissue and treat target tissue, or a first catheter100 a configured to expand tissue and a second catheter 100 b configuredto treat target tissue. In these embodiments, injectate 221 can comprisea material configured to enhance or otherwise modify a target treatmentstep. For example, injectate 221 can comprise a conductive fluid (e.g.an electrically conductive fluid), such as saline configured to modify asubsequent target tissue treatment by treatment element 139 a in whichRF or other electrical energy is delivered to target tissue (e.g. whentreatment element 139 a comprises an array of electrodes). Similarly,injectate 221 can comprise a chromophore or other light absorbingmaterial and/or a light scattering material configured to modify asubsequent target tissue treatment by treatment element 139 a in whichlight energy is delivered to target tissue (e.g. when treatment element139 a comprises a lens, one or more conduits 111 comprise an opticalfiber, and controller 250 comprises an energy delivery unit EDU 260comprising a laser).

In some embodiments, fluid delivery element 139 c comprises a needlewith two separate lumens (e.g. two lumens each fluidly connected to adifferent conduit 111), such that two different materials can beinjected into tissue without the two fluids mixing prior to entering thetissue. Alternatively, fluid delivery element 139 c can comprise twodifferent needles directed toward a similar area. Injectate 221 cancomprise a first material and a second material which form a hydrogelwhen mixed (e.g. the two materials crosslink to form an absorbablehydrogel). Alternatively or additionally, injectate 221 can comprisewater soluble PEG reactive end groups and an amino acid with reactiveend groups.

In some embodiments, injectate 221 comprises a material selected fromthe group consisting of: autologous fat; collagen; bovine collagen;human cadaveric dermis; hyaluronic acid; calcium hydroxylapatite;polylactic acid; semi-permanent PMMA; dermal filler; gelatin; andcombinations of one or more of these. In some embodiments, injectate 221comprises a material whose viscosity changes (e.g. increases) afterdelivery into tissue, such as a fluid whose viscosity increases as it isheated to body temperature.

In some embodiments, injectate 221 comprises a material including hollowmaterials and a carrier material, such as when system 10 is constructedand arranged to deliver injectate 221 to create a therapeuticrestriction. In these embodiments, injectate 221 can comprise a materialas described in US Patent Application US20080107744 or US PatentApplication US20110091564, the contents of each of which is incorporatedherein by reference in its entirety for all purposes. In someembodiments, injectate 221 comprises inorganic fibers and a carriermaterial. The inorganic fibers can be constructed and arranged toprevent or otherwise reduce their migration within tissue. The carriermaterial can be constructed and arranged to allow the inorganic fibersto be injectable (e.g. to pass through fluid delivery element 139 c). Inthese embodiments, injectate 221 can comprise a material as described inUS Patent Application US20140255458, the contents of which isincorporated herein by reference in its entirety for all purposes.

In some embodiments, system 10, console 200 and/or catheter 100 isconstructed and arranged to reduce risk during injection of materialinto the wall of the duodenum. In some embodiments, a pre-determinedvolume of polymer or other material is injected using catheter 100 or astandard endoscopic needle device. A volume of at least 1 ml or 2.5 mlof a first material (e.g. a relatively inert material such as sterilesaline), is injected into the wall first, creating a first expandedtissue volume, a “bleb” of expanded tissue and the saline. Subsequently,a second material, such as a pharmaceutical agent, a durable material(e.g. to create a therapeutic restriction as described herein), or otheractive material is injected into the first expanded tissue volume tofurther expand the tissue.

In some embodiments, system 10 includes a tool 500 comprising a vacuumapplying tool such as an endoscopic cap. Catheter 100 or a standardendoscopic needle device can inject a material into the wall of theduodenum while the endoscopic cap applies suction to the intestinalmucosa. A needle or other fluid delivery element of catheter 100 (e.g.fluid delivery element 139 c) or a needle of a standard endoscopicneedle device is delivered into intestinal tissue while the mucosa ofthe intestine is lifted by tool 500.

In some embodiments, injectate 221 comprises a system 10 or operatordetectable material such as a visualizable material, magnetic materialor other detectable material. In some embodiments, injectate 221comprises one or more materials (e.g. a biocompatible polymer orcopolymer such as ethylene vinyl alcohol), and can further include adetectable material selected from the group consisting of: a radiopaquematerial; barium sulfate; tantalum; ultrasonically reflecting material;magnetic material; a visible dye; and combinations of one or more ofthese. In these embodiments, system 10 can comprise a fluid extractionassembly comprising one or more ports 137 that are constructed andarranged to withdraw fluids from within the intestine, such as via oneor more conduits 111 and one or more pumping assemblies 225. One or morefunctional elements 109, 119, 139, 229 and/or 309 can comprise a sensorconfigured to produce a signal related to the quantity of injectate 221recovered via the one or more ports 137, such as a sensor configured todetect a volume, mass, flow rate and/or other parameter of injectate221. Signal processor 252 can be configured to assess tissue expansionbased on an analysis of the recovered injectate 221.

In some embodiments, injectate 221 comprises one or more materials suchas ethylene vinyl alcohol (EVOH) which is provided in a liquid solventsuch as dimethyl sulfoxide (DMSO). In these embodiments, a visualizablematerial such as a radiopaque material (e.g. tantalum) can be furtherincluded. In these embodiments, catheter 100 can be configured todeliver this injectate 221 into tissue (e.g. via one or more fluiddelivery elements 139 c), after which the one or more materials, and thevisualizable material if included, precipitate from the solution to forma spongy implant, which can remain in proximity to the injection sitefor a prolonged period of time.

In some embodiments, algorithm 251 is configured to determine anexpanded size for functional assembly 130, such as when system 10comprises multiple catheters 100 with different expanded diameters forfunctional assembly 130 and/or when the expanded diameter of functionalassembly 130 can be varied by system 10 (e.g. by varying pressure and/orvolume of fluid within functional assembly 130). In these embodiments,algorithm 251 can comprise a bias, such as a bias which tends towardlower diameters (e.g. rounds down to the next smaller size of afunctional assembly 130 available after calculating a target value). Insome embodiments, algorithm 251 is configured to select one catheter 100for use in a patient, by selecting one a kit of multiple catheters 100comprising one or more different parameters (e.g. one or more functionalassembly 130 parameters). In these embodiments, algorithm 251 can alsoinclude a bias, such as a bias toward choosing a smaller functionalassembly 130 (e.g. smaller length or smaller expanded diameter).

In some embodiments, algorithm 251 of console 200 comprises an imageanalysis algorithm configured to analyze one or more patient and/orsystem 10 images. For example, a tissue location can be analyzed priorto, during and/or after a desufflation (e.g. aspiration) step, such asto confirm adequate apposition of a functional assembly 130 with tissueof an axial segment of tubular tissue (e.g. an axial segment of theintestine). Algorithm 251 can comprise one or more image analysisalgorithms configured to assess various conditions including but notlimited to: apposition of functional assembly 130 with tissue (e.g.intestinal wall tissue); effectiveness of a desufflation procedure;effectiveness of an insufflation procedure; sufficiency of a tissueexpansion procedure; sufficiency of a tissue ablation procedure; andcombinations of one or more of these.

In some embodiments, one or more reservoirs 220 and/or one or morepumping assemblies 225 are constructed and arranged to provide acryogenic gas or other cryogenic fluid to functional assembly 130, suchas to perform a cryogenic ablation of target tissue and/or to cooltarget tissue that has been heated above body temperature. Cryogenic gascan be delivered through smaller diameter conduits 111 than would berequired to sufficiently accommodate a liquid ablative or neutralizingfluid, which correlates to a reduced diameter of shaft 110. Balloon 136can comprise a compliant balloon (e.g. a highly compliant balloon).Balloon 136 can be fluidly connected to multiple fluid transportconduits 111, singly or collectively providing inflow (i.e. delivery)and/or outflow (i.e. extraction) of the cryogenic gas. System 10 can beconfigured to control the pressure within balloon 136, such as at apressure sufficient, but not much greater than that which would berequired to simply inflate balloon 136. A highly compliant balloon 136can be configured to reduce or avoid the need for a luminal sizing stepto be performed. Temperature seen by the target tissue is driven by thetemperature of the fluid in balloon 136. During treatment (i.e.cryogenic ablation) the pressure in balloon 136 can be maintained at apressure at or below 20 inHg, such as below 18 inHg, 15 inHg or 10 inHg.

In some embodiments, system 10 comprises a first catheter 100 with afunctional assembly with a first diameter, and a second catheter 100with a functional assembly with a second diameter (e.g. a smallerexpanded diameter than the first diameter). In these embodiments, system10 can be constructed and arranged such that an operator (e.g. aclinician) inserts the first catheter 100 into the intestine of apatient and performs a first function, such as a function selected fromthe group consisting of: size (e.g. determine the diameter) of one ormore axial locations of intestine; perform or at least attempt toperform a tissue expansion procedure in one or more axial segments ofintestine; perform or at least attempt to perform a tissue treatment(e.g. tissue ablation) at one or more axial segments of intestine; andcombinations of one or more of these. In some embodiments, during and/orafter performance of the first function, a decision can be made toswitch to the second catheter 100 with a different functional assembly130, such as when it is determined the functional assembly 130 of thefirst catheter 100 is too large. In these embodiments, the firstcatheter 100 and the second catheter 100 can each be configured toperform both a tissue expansion procedure and an ablation procedure. Insome embodiments, the functional assembly 130 of the first catheter 100comprises an expanded diameter between 21 mm and 29 mm, such as adiameter between 23 mm and 27 mm, such as a diameter of approximately 25mm. In some embodiments, algorithm 251 is configured to select the firstcatheter 100 and/or the second catheter 100 for use (e.g. use in thepatient). Alternatively, the functional assembly 130 of the firstcatheter 100 can comprise an expanded diameter smaller than the expandeddiameter of the functional assembly 130 of the second catheter 100,wherein the second catheter 100 is introduced into the patient if it isdetermined that the expanded diameter of the functional assembly 130 ofthe first catheter 100 is too small.

In some embodiments, pumping assembly 225 comprises at least two pumpingassemblies 225 configured to propel fluid out of (i.e. extract fluidfrom) functional assembly 130 and/or another component of catheter 100,such as two pumping assemblies 225 which operate simultaneously duringthe performance of a functional assembly 130 drawdown procedure (e.g. anemergency radial contraction of functional assembly 130 that isinitiated during an undesired situation, such as an emergency drawdownprocedure initiated when a leak is detected). In some embodiments, twopumping assemblies 225 are configured to deliver fluid to functionalassembly 130 (e.g. to balloon 136 and/or one or more fluid deliveryelements 139 c) or other component of catheter 100. In theseembodiments, simultaneous fluid delivery can also be performed when aleak is detected, such as to simultaneously deliver a neutralizing fluidto tissue being undesirably exposed to ablative fluid. Alternatively oradditionally, a second pumping assembly 225 can be configured to beginfluid delivery and/or fluid extraction when the failure of a firstpumping assembly 225 is detected. Two or more pumping assemblies 225 canbe fluidly attached to one or more fluid transport conduits 211.

In some embodiments, console 200 is constructed and arranged to maintaina minimum volume (e.g. “level”) of one or more reservoirs 220. In someembodiments, console 200 is constructed and arranged to disable a pump225 if an undesired condition is detected, such as by a signal recordedby a functional element 229 a and/or 229 b that comprises a sensorconfigured to monitor one or more system parameters (e.g. temperature,pressure, flow rate, and the like).

In some embodiments, console 200 is constructed and arranged to limit atreatment time or to limit another treatment parameter. In theseembodiments, the treatment parameter can be limited by software, such assoftware of algorithm 251 and/or controller 250. Alternatively, thetreatment parameter can be limited by hardware (e.g. a hardware-basedalgorithm 251), such as hardware of controller 250 such as a temperaturecontrolled functional element which turns off a pumping assembly 225and/or otherwise prevents or reverses energy being delivered by afunctional assembly 130 of catheter 100.

In some embodiments, system 10 is constructed and arranged (e.g. viaalgorithm 251) to adjust one or more treatment parameters, such as anadjustment based on the expanded size of a functional assembly 130, suchas when system 10 comprises multiple catheters 100, each comprising adifferent expanded size of its functional assembly 130. In theseembodiments, system 10 can be constructed and arranged to adjust one ormore treatment parameters selected from the group consisting of:temperature of ablative fluid; volume of ablative fluid; pressure ofablative fluid; amount of energy delivered such as peak amount of energydelivered and/or cumulative amount of energy delivered; duration oftreatment; amount of fluid delivered into tissue (e.g. during a tissueexpansion procedure or a tissue ablation procedure); and combinations ofone or more of these.

In some embodiments, console 200 is constructed and arranged to providea first fluid at an ablative temperature, and a second fluid at aneutralizing temperature. For example, a first fluid can be provided bya first reservoir 220 such that the first fluid enters functionalassembly 130 at a sufficiently high temperature to ablate tissue, suchas at a temperature above 44° C. or above 60° C. A second fluid can beprovided by a second reservoir 220 such that the second fluid entersfunctional assembly 130 at a neutralizing temperature below bodytemperature, such as a temperature between room temperature and bodytemperature, or a temperature below room temperature. Alternatively, anablative fluid can comprise a fluid of sufficiently low temperature toablate tissue (e.g. below 5° C.), and an associated neutralizing fluidcan comprise a warmer fluid configured to reduce the tissue damagingeffects of the ablative fluid, as described herein. In some embodiments,a neutralizing fluid is provided to functional assembly 130 prior toand/or after delivery of ablative fluid to functional assembly 130, asdescribed in detail herebelow.

An ablative fluid and a neutralizing fluid can be transported tofunctional assembly 130 via the same or different conduits 111. Fluidcan be extracted from functional assembly 130 via the same or differentconduits used to deliver the first fluid and/or the second fluid. Insome embodiments, conduits 111 used to deliver and/or extract anablative fluid or a neutralizing fluid are configured to be translated(e.g. advanced and/or retracted), such that their distal end positionwithin or otherwise relative to functional assembly 130 can be varied.In some embodiments, one or more conduits 111 and/or functional assembly130 can be thermally primed prior to treating target tissue. In someembodiments, ablative fluid and/or neutralizing fluid is provided tofunctional assembly 130 in a recirculating manner. Alternatively,ablative fluid and/or neutralizing fluid can be provided to functionalassembly 130 as a bolus (non-circulating volume of fluid). In someembodiments, functional element 119 comprises one or more valvesconstructed and arranged to control the flow of fluid through one ormore conduits 111. In recirculating fluid embodiments, a conduit 111supplying fluid can be manually or automatically changed to a fluidextraction conduit, such as when a separate conduit 111 is configured tonormally extract fluid from functional assembly 130 becomes occluded,when a conduit 111 or functional assembly 130 begins to leak, orotherwise when it is desired to radially compact functional assembly 130at an accelerated rate.

In some embodiments, at least a first conduit 111 a provides ablativefluid to functional assembly 130 while at least a separate conduit 111 bsimultaneously withdraws ablative fluid from functional assembly 130,such as to recirculate ablative fluid within functional assembly 130. Inthese embodiments, functional assembly can be radially expanded (e.g.initially or after a radial compacting step), by filling functionalassembly 130 (e.g. with ablative fluid, neutralizing fluid and/or otherfluid) by using both first conduit 111 a and second conduit 111 b.

In some embodiments, treatment element 139 a comprises an energydelivery element including multiple layers of electrical conductors(e.g. conductors and/or semiconductors) configured to generate heat whenelectricity passes through one or more of the conductors. In theseembodiments, functional element 139 can be electrically connected to oneor more conduits 111 comprising one or more electrical wires. Functionalassembly 130 can comprise a compliant or non-compliant balloon ontowhich functional element 139 is positioned. Treatment element 139 a cancomprise electrical conductors created by depositing one or morecoatings on one or more substrates. When electricity is passed throughthe coating, heat is generated. The heat can be effectively transferredacross the whole surface of functional element 139 mainly throughconduction, but also via radiation and convection and into targettissue.

In some embodiments, balloon 136 comprises at least a porous portion ora portion otherwise constructed and arranged to allow material containedwithin balloon 136 to pass through at least a portion of balloon 136. Inthese embodiments, injectate 221 can comprise a material configured topass through at least a portion of balloon 136, such as a conductive gelmaterial configured to modify energy delivery, such as when treatmentelement 139 a comprises one or more electrodes configured to delivery RFenergy to target tissue. In other embodiments, agent 420 comprises oneor more agents configured to be delivered into balloon 136 and to passthrough at least a portion of balloon 136 and into the intestine.

In some embodiments, system 10 is constructed and arranged to deliverfluid into functional assembly 130 at a flow rate of at least 500ml/min, at least 1000 ml/min, at least 2000 ml/min, or at least 2500ml/min. In some embodiments, system 10 is constructed and arranged toextract fluid from functional assembly at a flow rate of at least 500ml/min, at least 750 ml/min, or at least 1000 ml/min. In someembodiments, system 10 is constructed and arranged to remove and extractfluids at approximately the same flow rate. In some embodiments, fluidin console 200 is provided to catheter 100 at a temperature of at least60° C., 70° C. or 80° C. In some embodiments, system 10 is configured totreat at least three axial segments of intestinal tissue, such as atleast three axial segments of tissue treated with a heat ablation and atleast one cooling step (e.g. a cooling step performed prior to and/orafter the heat ablation step).

In some embodiments, tool 500 comprises an insufflation and/ordesufflation tool, such as a catheter comprising a port (e.g. a distalopening) for delivering and/or extracting fluids from the intestine.Tool 500 can be insertable through the working channel of anintroduction device 50 (e.g. through an endoscope). Delivery ofinsufflation fluids can be performed to move tissue away from functionalassembly 130 and/or move tissue away from one or more functionalelements 139 or other parts of catheter 100. In some embodiments,insufflation is performed to stop or limit a transfer of energy totissue (e.g. in an emergency or insufflation-controlled ablation step).

In some embodiments, tool 500, catheter 100, introduction device 50and/or another component of system 10 comprises a pressure-neutralizingassembly constructed and arranged to modify the pressure within aluminal segment of the intestine (e.g. a luminal segment proximatefunctional assembly 130). In these embodiments, tool 500 and/or catheter100 can comprise one or more openings or other elements configured asvents, such as to vent the luminal segment to room pressure (e.g.clinical procedure room pressure) or otherwise maintain the pressure ina segment of the intestine below a threshold. In some embodiments,introduction device 50 comprises an endoscope comprising a biopsy portconfigured to vent the luminal segment to room pressure. Thepressure-neutralizing assembly can be configured to extract gas from theintestinal segment, and/or to maintain the pressure within theintestinal segment below a threshold. In some embodiments, venting isactivated automatically, such as when a pressure (e.g. as measured by asensor of the present inventive concepts) reaches a threshold (e.g. asdetermined by algorithm 251).

In some embodiments, algorithm 251 comprises a pressure algorithmconfigured to modify a system parameter based on a measured pressure,such as a modification made based on the pressure within a luminalsegment of the intestine in which functional assembly 130 is positionedor otherwise proximate (e.g. as measured or otherwise determined byanalysis of a signal provided by a sensor of catheter 100, bodyintroduction device 50 or another sensor of system 10 as describedherein. In these embodiments, system 10 can be configured to modify thevolume of fluid within functional assembly 130 and/or modify thepressure of functional assembly 130 based on the luminal segmentpressure.

In some embodiments, functional assembly 130 is positioned in an axialsegment of intestine, expanded to a diameter less than the averagediameter of the axial segment, and activated (e.g. to deliver energy totissue and/or fluids to tissue) during a contraction of the intestine.In these embodiments, the contraction of the intestine can be one ormore of: a (natural) peristaltic contraction; a contraction caused bystimulation (e.g. electrical or chemical stimulation by catheter 100and/or tool 500); a contraction caused during a desufflation procedure;and combinations of one or more of these. Contraction of the intestinecan comprise a desufflation procedure performed by a device selectedfrom the group consisting of: catheter 100; an endoscope or other bodyintroduction device 50; a second catheter inserted into the intestine;and combinations of one or more of these.

In some embodiments, tool 500 comprises a diagnostic tool, such as adiagnostic tool comprising a sensor. Tool 500 can be configured toperform a diagnostic test of the patient and/or a diagnostic test of allor a portion of system 10. Tool 500 can comprise a body-insertable tool.Tool 500 can be constructed and arranged to gather data (e.g. via anincluded sensor) related to a patient physiologic parameter selectedfrom the group consisting of: blood pressure; heart rate; pulsedistention; glucose level; blood glucose level; blood gas level; hormonelevel; GLP-1 level; GIP Level; EEG; LFP; respiration rate; breathdistention; perspiration rate; temperature; gastric emptying rate;peristaltic frequency; peristaltic amplitude; and combinations of one ormore of these.

Alternatively or additionally, tool 500 can comprise a tissue markingtool, such as a tissue marking tool configured to be deployed throughintroduction device 50 (e.g. an endoscope). In some embodiments, system10 comprises marker 430, which can comprise a dye or other visualizablemedia configured to mark tissue (e.g. using a needle-based tool 500),and/or a visualizable temporary implant used to mark tissue, such as asmall, temporary anchor configured to be attached to tissue by tool 500and removed at the end of the procedure (e.g. by tool 500) or otherwisepassed by the natural digestive process of the patient shortly afterprocedure completion. Tissue marker 430 can be deposited or deployed inreference to (e.g. to allow an operator to identify) non-target tissue(e.g. a marker positioned proximate the ampulla of Vater to bevisualized by an operator to avoid damage to the ampulla of Vater),and/or to identify target tissue (e.g. tissue to be ablated). In someembodiments, tissue marker 430 is deposited or deployed in reference totissue selected from the group consisting of: gastrointestinaladventitia; duodenal adventitia; the tunica serosa; the tunicamuscularis; the outermost partial layer of the submucosa; ampulla ofVater; pancreas; bile duct; pylorus; and combinations of one or more ofthese. In some embodiments, tissue marking is performed as describedherebelow in reference to FIG. 43.

In some embodiments, port 137 can be configured to engage tissue (e.g.when a vacuum is applied to port 137 via one or more conduits 111),after which target tissue can be treated by treatment element 139 a.Engagement of tissue by port 137 can be used to stretch or otherwisemanipulate tissue such that a safe and effective treatment of targettissue can be performed by treatment element 139 a, such as whentreatment element 139 a comprises fluid at an ablative temperature or anarray of electrodes configured to deliver RF energy. In theseembodiments, catheter 100 can be configured to treat target tissuewithout performing an associated tissue expansion procedure (e.g.without expanding tissue in proximity to the target tissue to betreated).

Functional assembly 130 can be configured to perform a medical procedure(e.g. a tissue expansion procedure and/or a tissue ablation or othertissue treatment procedure) on multiple axial segments of intestinaltissue. Two or more of the multiple axial segments can be treatedsequentially and/or simultaneously. The two or more of the multipleaxial segments can be relatively proximate each other, such as to sharecommon boundaries or avoid significant gaps in untreated tissue. Themultiple axial segments can comprise partial or full circumferentialsegments of intestinal tissue. The multiple axial segments cancumulatively comprise at least 3 cm in length or at least 6 cm inlength, such as when between 1 and 6 treatments (e.g. between 2 and 6treatments) are performed (e.g. functional assembly 130 is repositionedbetween 1 and 5 times). The multiple axial segments can cumulativelycomprise a length of at least 9 cm, such as when between 2 and 9treatments are performed (e.g. functional assembly 130 is repositionedbetween 1 and 8 times). In these embodiments, system 10 can beconfigured to treat diabetes, such as Type 2 diabetes. In someembodiments, system 10 is constructed and arranged to treat diabetes asdescribed in applicant's co-pending International Patent ApplicationSerial Number PCT/US2015/040775, entitled “Methods and Systems forTreating Diabetes and Related Diseases and Disorders”, filed Jul. 16,2015, the content of which is incorporated herein by reference in itsentirety for all purposes.

In some embodiments, system 10 is configured to initially expandfunctional assembly 130, with a fluid at a non-ablative temperature(e.g. a fluid configured to cool tissue without ablating it), afterwhich a fluid at an ablative temperature can be introduced intofunctional assembly 130 (e.g. a fluid at sufficiently high temperatureto ablate tissue).

In some embodiments, catheter 100 and/or another device of system 10comprises an anchoring element, such as when port 137 is configured toanchoringly engage tissue when a vacuum is applied to port 137 (e.g. viaone or more conduits 111). Alternatively or additionally, inflation ofballoon 136 can be used to anchor functional assembly 130 at aparticular intestinal location. One or more functional elements 139 cancomprise an anchor element, such as a high friction coating or surfacetreatment, or an extendable barb.

In some embodiments, system 10 is constructed and arranged to allow anoperator to position the functional assembly within an axial segment ofthe intestine and perform a first procedure on intestinal tissue withfunctional assembly 130. System 10 is further constructed and arrangedto anchor functional assembly 130 (prior to, during and/or after thefirst procedure). Subsequent to the performance of the first procedureand the anchoring of functional assembly 130, a second procedure isperformed. The first procedure can comprise a tissue expansionprocedure. The second procedure can comprise a tissue ablationprocedure, such as a tissue ablation procedure which ablates mucosaltissue within or otherwise proximate previously expanded submucosaltissue. Repeating of the three steps (i.e. the first procedure, theanchoring of functional assembly 130, and the second procedure) can beperformed at additional locations within the intestine.

As described herein, in some embodiments, catheter 100 or another deviceof system 10 such as catheter 30 of system 10 of FIG. 2, is constructedand arranged to perform a luminal sizing measurement (e.g. a measurementin which diameter and/or other cross sectional geometry is quantified),and produce luminal size information. In these embodiments, system 10can include multiple catheters 100, one of which is selected and/oradjusted based on the luminal size information. Alternatively oradditionally, system 10 can be configured to adjust one or more systemparameters based on the luminal size information, such as a consolesetting 201 selected from the group consisting of: volume of fluiddelivered into functional assembly 130; flow rate of fluid deliveredinto functional assembly 130; temperature of fluid delivered intofunctional assembly 130; pressure of functional assembly 130; andcombinations of one or more of these.

In some embodiments, console 200 and system 10 are constructed andarranged to maintain functional assembly 130 of catheter 100 at or belowa target level of a functional assembly 130 parameter, such as at orbelow a target diameter, pressure and/or volume for functional assembly130. In some embodiments, functional assembly 130 is maintained below atarget pressure of 0.9 psi (e.g. during a tissue expansion, tissueablation and/or other tissue treatment step).

In some embodiments, catheter 100 and system 10 are constructed andarranged to compensate for muscle contraction of the intestine (e.g.peristalsis within the intestine). For example, algorithm 251 can beconfigured to actively regulate a functional assembly 130 parameter (e gdiameter, pressure within and/or flowrate to and/or from), such as whenalgorithm 251 anticipates, recognizes and/or compensates for muscularcontraction of the intestine. In some embodiments, expansion offunctional assembly 130 can be timed to occur during the bottom (lowerrange) of a muscular contraction (e.g. peristalsis) cycle.

In some embodiments, catheter 100 and system 10 are constructed andarranged to perform a medical procedure in the intestine that issynchronized with one or more muscular contractions of the intestine,such as one or more peristaltic contractions used to contact intestinalwall tissue with an expanded or partially expanded functional assembly130.

In some embodiments, system 10 is constructed and arranged to size alumen of a first axial segment of the intestine. System 10 can befurther constructed an arranged to subsequently perform a tissueexpansion of a portion of the first axial segment (e.g. a full orpartial circumferential segment of the submucosa of the axial segment),by injecting fluid (e.g. a fixed volume of fluid) into tissue within orproximate the first axial segment. System 10 can be further constructedand arranged to subsequently perform a luminal sizing measurement of thefirst axial segment. System 10 can be further constructed and arrangedto subsequently perform a target tissue treatment of the first axialsegment (e.g. a treatment of a full or partial circumferential segmentof the mucosal tissue of the first axial segment). The treatmentperformed by system 10 can comprise one or more treatment parameters(e.g. one or more ablation parameters) that are based on the luminalsizing measurement performed after tissue expansion, and determined viaalgorithm 251.

In some embodiments, system 10 comprises one or more first catheters 100a, each with a first functional assembly 130 a of a particular size andconfigured to treat target tissue. System 10 further comprises one ormore second catheters 100 b, each with a functional assembly 130 b andconfigured to perform a tissue expansion procedure. System 10 can beconstructed and arranged to size a lumen of one or more axial segmentsof intestine (e.g. using a catheter 100 or other luminal sizing deviceas described herein) to determine the diameter at a relatively narrow(e.g. the smallest diameter) location within the one or more axialsegments to be treated. System 10 is further constructed and arranged toselect a first catheter 100 a based on the luminal sizing information(e.g. using algorithm 251). System 10 can be constructed and arranged toinflate or otherwise expand the functional assembly 130 a of a catheter100 a (e.g. with an ablative fluid) to a diameter related to thesmallest diameter location. System 10 can be constructed and arranged toinflate or otherwise expand the functional assembly 130 b of a catheter100 b (e.g. with a gas) to a diameter corresponding to the expandeddiameter of the selected catheter 100 a (e.g. a diameter less than theproximate axial segment lumen size and/or to a diameter related to thesmallest diameter location). System 10 can be constructed and arrangedto apply a vacuum to one or more ports 137 of catheter 100 b to engageneighboring tissue. System 10 can be further constructed and arranged toinject fluid into tissue (e.g. submucosal tissue) until the pressurewithin the associated functional assembly 130 b exceeds a threshold,such as a threshold of 0.3 psi, 0.5 psi or 0.7 psi (e.g. but below asecond threshold of 2.0 psi or 4.0 psi). System 10 can be constructedand arranged to subsequently disengage functional assembly 130 b fromthe tissue (e.g. by removal of the vacuum from each port 137), andradially collapse balloon 136 (e.g. via extraction of fluid from balloon136 via one or more conduits 111 of catheter 100 b). System 10 can beconstructed and arranged to similarly expand tissue at one or more otheraxial segments of the intestine. System 10 can be constructed andarranged to treat target tissue of the one or more axial segments (withexpanded tissue) using the particular first catheter 100 a whoseexpanded diameter was chosen based on the minimum diameter of the one ormore axial segments. In some embodiments, multiple tissue expansionprocedures are performed by catheter 100 b sequentially, after which aseries of target tissue treatments (e.g. tissue ablations) are performedby catheter 100 a sequentially. Alternatively, a pattern of alternatingbetween one or more tissue expansions and one or more tissue treatmentscan be performed.

In some embodiments, system 10 comprises one or more first catheters 100a, each with a first functional assembly 130 a of a particular size andconfigured to treat target tissue. System 10 can further comprise one ormore second catheters 100 b, each with a functional assembly 130 b andconfigured to perform a tissue expansion procedure. System 10 can beconstructed and arranged to size a lumen of one or more axial segmentsof intestine (e.g. using a catheter 100 or other luminal sizing deviceas described herein) to determine the diameter at a relatively narrow(e.g. the smallest diameter) location within the one or more axialsegments. System 10 can be further constructed and arranged to select afirst catheter 100 a based on the luminal sizing information (e.g. usingalgorithm 251). System 10 is further constructed and arranged to inflatethe functional assembly 130 b of a catheter 100 b (e.g. with a gas) to apressure sufficient to correlate to sufficient apposition with the axialsegment luminal wall. System 10 can be further constructed and arrangedto apply a vacuum to one or more ports 137 of catheter 100 b to engageneighboring tissue. System 10 can be further constructed and arranged toinject fluid into tissue (e.g. submucosal tissue) until the pressurewithin the associated functional assembly 130 b exceeds a threshold, atwhich time fluid (e.g. air) can be extracted from functional assembly130 b and fluid delivery by fluid delivery element 139 c continues untilthe volume of functional assembly 130 b reaches a pre-determined lowerlimit.

As described hereabove, system 10 can be constructed and arranged toablate or otherwise treat tissue with an expanded functional assembly130 that is smaller than the native lumen diameter of an axial segmentof intestine. The amount of fluid injected to expand tissue (e.g.submucosal tissue) can be determined in a closed-loop manner to achievea post-expansion lumen size with a specific diameter along one or moreaxial segments of the intestine (e.g. the duodenum). System 10 cancomprise a single functional assembly 130 configured to treat (e.g.ablate) multiple axial segments of intestine, each with a pre-expandedtissue layer (e.g. submucosal tissue layer expanded to a diameterapproximating or otherwise related to the diameter of the expandedfunctional assembly 130). System 10 can comprise a functional assembly130 configured to treat (e.g. ablate) multiple axial segments ofintestine that are selected prior to the performance of tissue layerexpansion, such as to reduce overall procedure time and/or time betweentissue expansion and tissue treatment. System 10 can be constructed andarranged such that the difference between the native intestinal lumendiameter and the post-tissue expansion lumen diameter is known, such asto confirm acceptability of the tissue expansion step(s) prior to anablation step being performed. System 10 can be constructed and arrangedto eliminate one or more sizing steps, as described hereabove.

In some embodiments, system 10 is constructed and arranged to perform amedical procedure comprising a tissue treatment procedure for treating apatient disease or disorder, and the amount of tissue treated is basedon the severity of the patient's disease or disorder (e.g. amount oftissue treated is proportional to the severity). In some embodiments,the disease treated is diabetes, and the severity is determined bymeasuring one or more of: HbA1c level; fasting glucose level; andcombinations of one or more of these. In some embodiments, algorithm 251is configured to determine the amount of tissue to be treated based onthe severity of the patient's disease or disorder.

In some embodiments, system 10 is constructed and arranged to (e.g. viaalgorithm 251) to introduce fluid into functional assembly 130 (e.g.into a balloon 136 of functional assembly 130) until sufficientapposition against an intestinal wall is achieved (e.g. as determined bya pressure measurement and/or image analysis provided by a sensor of thepresent inventive concepts). Subsequently, fluid is extracted fromfunctional assembly 130 (e.g. until a second, lesser volume of fluidresides within functional assembly 130), after which the intestinal wallis contracted (e.g. via desufflation as described herein) such that theintestinal wall again contacts functional assembly 130. In theseembodiments, system 10 can operate as described herebelow in referenceto FIG. 38 or 40.

In some embodiments, desufflation is accomplished by applying vacuum toa port (e.g. one or more ports configured to remove fluid from theintestine, such as port 137, one or more ports of shaft 110 proximal ordistal to functional assembly 130 (e.g. port 112 a and/or 112 bdescribed herebelow in reference to FIG. 5B) and/or a lumen of anendoscope or other introduction device 50).

In some embodiments, functional assembly 130 is anchored to theintestine (e.g. by expanding functional assembly 130 and/or by havingport 137 engage tissue). In these embodiments, a tissue expansionprocedure can be performed, such as by advancing at least one fluiddelivery element 139 c (e.g. at least three fluid delivery elements 139c) into tissue and delivering injectate 221 (e.g. into submucosaltissue). Alternatively or additionally, a tissue ablation procedure canbe performed.

In some embodiments, system 10 is configured to deliver injectate 221into tissue, such as via one or more fluid delivery elements 139 c, eachof which can be positioned in a port 137. The delivery of injectate 221into tissue can produce a therapeutic restriction, occlude one or morebody conduits (e.g. blood vessels), deliver a (single) bolus of drug orother agent into blood or other tissue, create a drug or other agent“depot” in tissue, and combinations of one or more of these. Injectate221 can be configured to expand after delivery into tissue. Injectate221 can be configured to remain relatively “in place” within tissueproximate the injection site for at least 1 month, 3 months, 6 months,or 1 year. Injectate 221 can be delivered into tissue (e.g. via fluiddelivery element 139 c) in a location selected from the group consistingof: lower stomach; pylorus; proximal small intestine; distal smallintestine; duodenum; jejunum; terminal ileum; bowel; and combinations ofone or more of these. In some embodiments, injectate 221 comprises ahydrogel, such as to create a hydrogel prosthesis within one or moretissue layers of the intestine (e.g. one or more submucosal tissuelayers).

Injectate 221 can be delivered into tissue to create a therapeuticrestriction, as described herein, such as to create a space occupyingobstruction as a treatment for obesity, type 2 diabetes;hypercholesterolemia, hypertension; non-alcoholic fatty liver disease;non-alcoholic steatohepatitis; and/or other metabolic disease. Injectate221 can be delivered to one or more tissue locations to create a senseof satiety, reduce chime throughput and/or reduce obesity. Injectate 221can be injected into the gastric varices, such as when injectate 221comprises an occlusive agent such as an adhesive such as cyanoacrylate.System 10 can be constructed and arranged such that delivery ofinjectate 221 into one or more tissue locations alters nutrientabsorption and/or hormonal signaling from the mucosa. System 10 can beconstructed and arranged to deliver injectate 221 into colon tissue(e.g. to expand colon submucosal tissue), such as to treat fecalincontinence.

As described above, system 10 can be constructed and arranged to deliverinjectate 221 into tissue to deliver a bolus of medication and/or tocreate a drug or other agent depot within tissue of the patient, such aswithin mucosal tissue and/or submucosal tissue of the intestine. In someembodiments, an injectate 221 positioned within tissue is activatedbased on one or more signals produced by a sensor, such as a bioactiveglucose sensor that responds to the detection of an analyte and leads to(e.g. via one or more components of system 10) release or otheractivation of injectate 221. For example, injectate 221 can comprise ananti-diabetic agent, such as insulin, and a sensor (e.g. implant 192configured as a sensor) can comprise a glucose sensor that detects aglucose change, such as the higher glucose levels that occur after ameal. Injectate 221 can comprise a drug or other agent selected from thegroup consisting of: a steroid; an anti-inflammatory agent; achemotherapeutic; a proton pump inhibitor; a sclerosant agent; adifferentiation factor such as trans-retinoic acid; ananti-hyperglycemic agent such as GLP-1 analogue or others; ananti-obesity agent; an anti-hypertensive agent; an anti-cholesterolagent such as a statin or others; and combinations of one or more ofthese. In some embodiments, injectate 221 comprises a steroid or otheranti-inflammatory agent delivered to a therapeutic restriction of thepresent inventive concepts (e.g. delivered into an existing restrictionor to create a restriction). In some embodiments, injectate 221comprises one or more steroids and/or other anti-inflammatory agentsdelivered to the site of chronic inflammation, such as a site ofulcerative colitis or Crohn's disease. In some embodiments, injectate221 comprises one or more steroids or other anti-inflammatory agentsdelivered at the site of celiac disease (e.g. the proximal smallintestine) and/or otherwise delivered to treat celiac disease. In someembodiments, injectate 221 comprises one or more chemotherapeutic agentsdelivered to the site of a cancerous or pre-cancerous lesion.

Injectate 221 can be injected into tissue in a single procedure ormultiple procedures. System 10 can be configured to determine aninjectate 221 delivery parameter (e.g. determined by algorithm 251),such as by performing an analysis based on a patient demographicparameter and/or a patient physiologic parameter, such as age, weight,HbA1c level and cholesterol level. The injectate delivery parameter cancomprise a parameter selected from the group consisting of: volume ofinjectate 221 delivered; length and/or area of a tissue layer receivinginjectate 221; type of material included in injectate 221; viscosity ofinjectate 221; titration result of injectate 221; and combinations ofone or more of these.

In some embodiments, system 10 is constructed and arranged to bothdeliver a durable injectate 221 (e.g. injectate 221 remains in place forat least 1 month), as well as treat target tissue (e.g. a treatmentcomprising ablating duodenal and/or other intestinal mucosa). The twoprocedures can be performed on the same day or on different days.

In some embodiments, injectate 221 comprises a radiographic material,such as tantalum, such as to be used in combination with X-ray orfluoroscopy to assess tissue expansion (e.g. submucosal tissueexpansion), as described herein. Alternatively or additionally,injectate 221 can comprise a material that is visualizable under otherimaging modalities (e.g. an imaging modality provided by imaging device55), such as magnetic material; ferrous material; ultrasonicallyreflective material; and combinations of one or more of these.

In some embodiments, sensor 139 b comprises a sensor configured toprovide an impedance measurement, such as an impedance measurement usedby algorithm 251 to enable closed-loop or otherwise adjust delivery ofRF energy from treatment element 139 a. In some embodiments, injectate221 comprises a conductive substance, such as a conductive substanceconfigured to enhance an impedance measurement recorded by sensor 139 b.In these embodiments, injectate 221 can comprise one or more substancesthat are both conductive and visualizable (e.g. visualizable by imagingdevice 55 as described hereabove), such as tantalum.

In some embodiments, injectate 221 comprises a pharmaceutical drug orother agent (e.g. injectate 221 comprises agent 420) configured toprovide a therapeutic benefit when delivered by one or more fluiddelivery elements 139 c into intestinal or other tissue. In theseembodiments, injectate 221 can be injected into mucosal tissue and/ortissue proximate mucosal tissue (e.g. submucosal tissue). A majorfunction of the mucosa is to bind or absorb certain molecules, andprevent or otherwise reduce the passage of all other molecules. Thus,insertion of injectate 221 directly into the submucosa can bypass themucosal barrier, enabling the delivery of therapeutic large moleculesthat otherwise would be passed through the body completely or largelyunabsorbed. This procedure also provides more precise dosage control,since the amount of absorption through the mucosa can be variable.Injectate 221 (e.g. injectate 221 comprising agent 420) can comprise anytherapeutic biologic or biochemical entity. The entity of injectate 221can have therapeutic effect by itself or it can be externally triggered,such as when injectate 221 comprises trigger materials, such as magneticnanoparticles triggered by magnetic fields, gold nanoparticles triggeredby light, optical or other fields, particles activated by light such asultraviolet light or infrared light, and/or particles activated byheating or chilling. In some embodiments, tool 500 is configured toprovide the triggering event, such as by generating a magnetic field,delivering light, and/or by delivering or extracting heat.

Local administration of drugs with high systemic toxicity and/orpropensity for resistance by catheter 100 is advantageous, as muchhigher local concentrations of the drug and/or much lower systemicbioavailability can be achieved. Avoidance of skin-penetratinginjections can be beneficial (e.g. avoiding associated pain, cosmeticissues and likely trauma to injection site). Catheter 100 can be used todeliver depot formulations of drugs or other agents to intestinal tissue(e.g. the intestinal submucosa) for the treatment of various GI orsystemic illnesses. Submucosal delivery via catheter 100 can avoid thelimitations associated with the mucosal barrier as described hereabove,and the limited bioavailability that is created. Submucosal delivery viacatheter 100 can also allow the delivered drug to avoid chemicalreactions or other adverse effects that result from interaction withvarious microbiological and pH environments in the patient's gut. Insome embodiments, injectate 221 comprises an anti-reflux medicationand/or an anti-acid medication, such as when injectate 221 is deliveredinto the mucosa or submucosa of the esophagus, intestine and/or stomach.

Systemic pharmaceutical therapy including immunomodulators to treatinflammatory bowel disease has issues with toxicity associated withimmune suppression. This systemic therapy can also have limited efficacyonce an individual develops antibodies against the monoclonal antibodytherapies. In both cases, high systemic concentrations of the drugslimit the ability to achieve sufficiently effective doses in the GItract itself, where the therapy needs to be most effective. A catheter100 comprising one or more fluid delivery elements 139 c can be used asa tool to perform site-specific delivery of drugs and other agents totreat GI illnesses, such as celiac disease and inflammatory boweldisease.

In some embodiments, system 10 comprises an implantable device, such asimplant 192 shown Implant 192 can comprise a medical device, such as adrug delivery depot or other drug delivery device. Implant 192 cancomprise a sensor or sensing device. In some embodiments, system 10 isconfigured to deliver implant 192 via a functional element 139, such asfluid delivery element 139 c (e.g. when fluid delivery element 139 ccomprises a needle comprising a lumen through which a sensor-basedimplant 192 can be deployed into tissue such as mucosal tissue,submucosal tissue, other intestinal tissue and/or other tissue of thepatient). In some embodiments, system 10 is constructed and arranged todeliver one or more implants 192 into tissue that is not proximate to asignificant number of pain-sensing nerves. In some embodiments, implant192 can comprise a sensor configured to measure a physiologic parameterselected from the group consisting of: blood pressure; heart rate; pulsedistention; glucose level; blood glucose level; blood gas level; hormonelevel; GLP-1 level; GIP Level; EEG; LFP; respiration rate; breathdistention; perspiration rate; temperature; gastric emptying rate;peristaltic frequency; peristaltic amplitude; and combinations of one ormore of these.

In some embodiments, implant 192 comprises a sensor, such as a sensorconfigured to be implanted in the submucosal tissue of the intestine. Insome embodiments, catheter 100 is configured to implant 192 into tissuevia a fluid delivery element 139 c and/or another functional element ofcatheter 100. Implant 192 can comprise a sensor configured to produce asignal related to a physiologic parameter related to the concentrationof a material selected from the group consisting of: fat, sugar (e.g.glucose or fructose); protein; one or more amino acids; and combinationsof one or more of these. In some embodiments, implant 192 comprises awireless communication element, such as an RF or infrared elementconfigured to transmit information (e.g. to a receiving component ofsystem 10). System 10 can be configured to analyze the receivedinformation, such as an analysis performed by algorithm 251 used tomanage obesity, insulin resistance and/or Type 2 diabetes.

In some embodiments, system 10 is constructed and arranged to expandtissue by delivering injectate 221 into tissue (e.g. submucosal tissueof the intestine) with fluid delivery element 139 c. System 10 can beconstructed and arranged to deliver injectate 221 at a constant orvaried rate, in open loop or closed loop delivery configurations. Insome embodiments, system 10 is configured to deliver fluid at anelevated flow rate and/or at an elevated pressure, such as with a flowrate and/or pressure which decreases over time. System 10 can beconstructed and arranged to monitor one or more pressures achievedduring delivery of injectate 221 into tissue. System 10 can beconfigured to measure a pressure using a pressure sensor-basedfunctional element 109, 119, 139, 209, 229 and/or 309. Alternatively oradditionally, system 10 can comprise a sensor positioned in tissueproximate the tissue to be expanded. In some embodiments, catheter 100comprises multiple fluid delivery elements 139 c, such as an array ofthree fluid delivery elements 139 c equally spaced about functionalassembly 130. In these embodiments, injectate 221 can be delivered intotissue by the multiple fluid delivery elements 139 c simultaneously orsequentially. Pressure measured by system 10 can correlate to thequality of tissue expansion, or other tissue expansion parameter. Insome embodiments, system 10 regulates delivery of injectate 221 (e.g. byregulation of one or more pumps 225 delivering injectate 221), and/ordetects an undesired state in the delivery of injectate 221, based onpressure measured by system 10. System 10 can be configured to confirmthat during delivery of injectate 221, a proper pressure increase occursin the expanded tissue, within functional assembly 130 and/or at anothersystem 10 location. The pressure at a first location can be measureddirectly (e.g. via a pressure sensor-based functional element locatedproximate the first location, or indirectly such as via a pressuresensor-based functional element located at a second location whosepressure can be correlated to the pressure at the first location, asdescribed herein for measurement of pressure, temperature and/or anysystem 10 parameter). System 10 can prevent a pressure threshold frombeing surpassed at one or more locations, such as to prevent anundesired event such as an amount and/or location of expansion of tissuethat can have a deleterious effect, such as expansion of serosal tissueof the intestine. In some embodiments, pressure information is processed(e.g. via algorithm 251), such that cumulative pressure information(e.g. time at pressure, pressure change rates, and the like) can becompared to one or more thresholds. In these embodiments, pressureinformation and/or processed pressure information (herein “pressureinformation”) can be used to confirm size or geometric shape of expandedtissue, such as to confirm full circumferentiality of a tissueexpansion. In some embodiments, system 10 correlates one or morepressure readings below a threshold to an adverse event selected fromthe group consisting of: fluid delivery element 139 c not deliveringfluid into the appropriate tissue (e.g. fluid delivery element 139 c hasnot properly penetrated tissue); failure of a functional element such asfailure of a functional element comprising a valve; leak in a conduitsuch as a leak in a conduit 111, 211, 212 and/or 311; and combinationsof one or more of these.

In some embodiments, functional assembly 130 is expanded with fluid at afirst pressure (e.g. a pressure of approximately 0.5 psi, 0.7, psi or0.9 psi), and fluid is delivered into tissue by one or more fluiddelivery elements 139 c (e.g. three fluid delivery elements 139 c).During fluid injection, system 10 can monitor pressure (e.g. a sensor ofthe present inventive concepts monitors pressure within functionalassembly 130 and/or within a conduit in fluid communication withfunctional assembly 130), and if the pressure exceeds a second pressure(e.g. a pressure of at least 0.7 psi, 0.9 psi 1.1 psi, or other pressuregreater than the first pressure), system 10 can reduce the pressurewithin the functional assembly 130 (e.g. reduce the pressure to thefirst pressure).

In some embodiments, system 10, console 200 and/or catheter 100 areconstructed and arranged to perform partial circumferential tissueexpansion of one or more axial segments of the GI tract (e.g. less than360° expansion of submucosal tissue of one or more axial segments of theintestine). In some embodiments, injectate 221 comprises a relativelyviscous material and catheter 100 delivers injectate 221 to create focal(i.e. partial circumferential) or multi-focal expansions of tissue (e.g.multiple partial circumferential expansions of submucosal tissue). Insome embodiments, a therapeutic restriction or other tissue expansion ofthe present inventive concepts can comprise two or more focalrestrictions created around the circumference of an axial segment oftubular tissue that block more than 50% or more than 75% of the luminaldiameter. In some embodiments, a full or near-full circumferentialexpansion of tissue is created by first expanding (e.g. inflating) afunctional assembly 130 and creating one or more focal expansions,subsequently compacting (e.g. deflating) the functional assembly 130,re-expanding (e.g. re-inflating) the functional assembly 130 andcreating additional focal expansions between the previously expandedareas to create a substantially circumferential expansion. Prior tore-expanding, functional assembly 130 can be repositioned (e.g.rotated). The compacting and re-expanding can be configured to allowmultiple fluid delivery elements 139 c to self-reposition during contactwith the peaks of the focal expansions (e.g. reposition into valleys inbetween the focal expansions). Alternatively, the functional assembly130 (e.g. shaft 110 of the catheter 100) can be rotated and/or otherwiserepositioned (e.g. automatically and/or manually) after the initialfocal expansions.

In some embodiments, functional assembly 130 comprises an expandeddiameter of a magnitude (e.g. a small enough diameter) configured toaccommodate a range of luminal diameters of the small intestine.Desufflation of the duodenum (e.g. using body introduction device 50 anddesufflation techniques known to those of skill in the art) can beperformed to collapse the inner wall of the intestine onto a fullyexpanded functional assembly 130. Functional assembly 130 can compriseone or more ports 137 configured to desufflate to collapse the innerwall of the intestine onto functional assembly 130. In some embodiments,shaft 110 or another component of catheter 100 comprises one or moreports configured to perform desufflation, such as ports 112 a and/or 112b described herebelow in reference to FIG. 5B. In some embodiments,system 10 comprises a separate desufflation tool (e.g. aspiration tool),such as tool 500 constructed and arranged to extract fluid from asegment of intestine, such as a segment comprising functional assembly130. In these embodiments, tool 500 can comprise one or more holes,slots, slits or other openings (e.g. positioned in a distal portion oftool 500) that are configured to aspirate fluids from the intestine,such as to collapse the inner wall of the intestine onto a fullyexpanded functional assembly 130.

In some embodiments, system 10 is configured to work in combination witha patient care practice, such as a patient diet that is maintained priorto and/or after performance of a medical device or diagnostic procedureperformed using system 10. For example, a patient diet or other patientpractice can be included prior to and/or after a tissue treatmentprocedure performed by system 10 to slow down healing (e.g. mucosalhealing) and/or provide another enhancement to the therapy achieved. Insome embodiments, mucosal healing is slowed down by a functional element139, tool 500 and/or other component of system 10. In some embodiments,regrowth of treated mucosal tissue is enhanced by a pre-proceduraland/or post-procedural patient diet. The diet can include: a liquid dietfor at least one day; a low sugar diet and/or a low fat diet for atleast one week; a standardized diabetic diet for at least 1 week; and/ornutritional counseling for at least 1 week.

In some embodiments, injectate 221 comprises an injectate configured tocause inflammation of tissue. In these embodiments, one or more fluiddelivery elements 139 c can be configured to deliver the injectate 221to tissue to cause an inflammatory response in the tissue. Theinflammatory response can result in a tissue layer that functions as aprotective layer during a subsequent tissue treatment procedure (e.g.tissue ablation procedure) performed by a functional assembly 130 ofcatheter 100.

In some embodiments, system 10 includes a tool 500 comprising a mucusremoval assembly constructed and arranged to remove mucus from one ormore intestinal wall locations (e.g. a full or partial circumferentialsegment of intestine), such as to remove mucus prior to a tissuetreatment performed by functional assembly 130. Alternatively oradditionally, functional assembly 130, one or more functional elements139 and/or one or more other components of catheter 100 can beconstructed and arranged to similarly remove mucus. In some embodiments,mucus is removed mechanically. Alternatively or additionally, mucus isremoved by delivery (e.g. via one or more fluid delivery elements 139 c)of agent 420 to a tissue surface (e.g. when agent 420 comprises amucolytic agent).

In some embodiments, system 10 comprises one or more materials ordevices configured to modify tissue healing, such as when catheter 100is constructed and arranged to treat intestinal mucosa (e.g. duodenalmucosa). For example, injectate 221, or implant 192 can be delivered inand/or proximate target tissue, such as at a time prior to, duringand/or after target tissue treatment. In these embodiments, for example,injectate 221, agent 420 and/or implant 192 that is delivered (e.g. byfluid delivery element 139 c or another component of catheter 100) canbe configured to delay healing of treated tissue in the intestine, suchas to provide enhanced therapeutic benefit to the patient and/or prolongthe benefit (e.g. enhance or prolong HbA1c reduction). In someembodiments, injectate 221, agent 420 and/or implant 192 comprises amaterial selected from the group consisting of: a chemotherapeuticagent; a cytotoxic agent; 5Fluorouracil; Mitomycin-c; Tretinoin topical(Retin-A, Retin-A Micro, Renova); Bleomycin; Doxorubicin (Adriamycin);Tamoxifen; Tacrolimus; Verapamil (Isoptin, Calan, Verelan PM);Interferon alfa-2b; Interferon beta 1a (Avonex, Rebif); Interferonalfa-n3 (Alferon N); Triamcinolone (Aristospan, Kenalog-10); Imiquimod(Aldara, Zyclara); and combinations of one or more of these.

In some embodiments, system 10 includes pressure neutralizing assembly72, which can be constructed and arranged to monitor and/or adjust (e.g.automatically or semi-automatically) the pressure within a segment ofthe intestine, such as to allow one or more therapeutic or diagnosticprocedures to be performed by functional assembly 130 at a particularpressure or within a particular range of pressures. Pressureneutralizing assembly 72 can be configured to deliver or extract fluidsfrom a segment of the intestine, such as to perform an insufflationprocedure, a desufflation procedure, or to otherwise modify the pressurewithin the segment of the intestine proximate functional assembly 130.

In some embodiments, system 10 includes body core cooling device 73,which can be constructed and arranged to cool the patient's bodytemperature (e.g. core body temperature). For example, body core coolingdevice 73 can be configured to cool one or more portions of the patientduring a tissue ablation or other procedure performed by catheter 100 asdescribed herein. Body cooling device 73 can be constructed and arrangedto cool the patient's blood (e.g. via an external blood circulationcircuit), intestine, and/or other body location, such as by extractingheat from one or more body locations. Body cooling device 73 cancomprise an elongate shaft for positioning in the esophagus. In someembodiments, body cooling device 73 is used to reduce the patient's corebody temperature prior to performance of one or more ablation proceduresperformed by functional assembly 130 of catheter 100.

In some embodiments, system 10 is constructed and arranged to produce animage (e.g. an image produced by an imaging device and/or other sensorof the present inventive concepts), such as is described herebelow inreference to FIG. 19 and FIGS. 29A-D. Algorithm 251 can be configured toanalyze one or more images of tissue that are visualized through one ormore portions of functional assembly 130, such as to determine the levelof tissue expansion and/or a level of tissue ablation, such as to assesscompletion adequacy of one or more steps of a medical procedure.

Referring now to FIG. 2, a schematic view of a system and device forperforming a medical procedure on the small intestine of a patient isillustrated, consistent with the present inventive concepts. System 10can comprise one or more components of similar construction andarrangement to similar components of system 10 of FIG. 1 describedhereabove. System 10 comprises catheter 100 and console 200. Catheter100 is constructed and arranged to treat target tissue, such as via thedelivery of energy and/or an ablating agent to target tissue. Catheter100 includes port 103 which operably attaches to port 203 of console200. In some embodiments, system 10 further comprises tissue expansioncatheter 20 which is constructed and arranged to expand one or morelayers of tissue, such as one or more layers of target tissue and/or oneor more layers of tissue proximate target tissue (e.g. one or morelayers of safety-margin tissue as described herein). In someembodiments, system 10 further comprises lumen diameter sizing catheter30 which is constructed and arranged to collect information correlatedto the diameter of a portion of tubular tissue (e.g. one, two or morediameters of a GI lumen within and/or proximate target tissue). In someembodiments, system 10 comprises multi-function catheter 40, which isconstructed and arranged to perform two or more functions selected fromthe group consisting of: tissue treatment (e.g. tissue ablation); tissueexpansion; luminal diameter sizing; and combinations of one or more ofthese. In some embodiments, system 10 comprises multi-function catheter40, and does not include one or more of: catheter 100, tissue expansioncatheter 20 and/or sizing catheter 30.

System 10 can further comprise a body introduction device, such as avascular introducer, laparoscopic port, and/or endoscope 50 a. System 10can further comprise one or more guidewires, such as guidewires 60 a and60 b (singly or collectively guidewire 60). In some embodiments, one ormore guidewires 60 comprise a guidewire selected from the groupconsisting of: a Savary-Gilliard® 400 cm guidewire, a Dreamwire™guidewire; a super stiff Jagwire™ guidewire; and/or a similar guidewire.In some embodiments, system 10 includes scope attached sheath 80. Sheath80 can comprise an elongate hollow tube which attaches (e.g. in aside-by-side manner) at one or more points along endoscope 50 a. Sheath80 can attach to endoscope 50 a along a majority of its length. In someembodiments, sheath 80 comprises the Reach® overtube manufactured byU.S. Endoscopy, or similar.

Catheter 100, tissue expansion catheter 20, lumen diameter sizingcatheter 30 and multi-function catheter 40 comprise handles 102, 22, 32and 42, respectively. Handles 102, 22, 32 and 42 each comprise one ormore controls, controls 104, 24, 34 and 44, respectively. Controls 104,24, 34 and 44 are configured to allow an operator to control one or morefunctions of the associated device, such as a function selected from thegroup consisting of: inflate or otherwise expand a functional assembly(e.g. functional assembly 130); deliver energy; modify energy delivery;deliver an insufflation fluid; insufflate a portion of the GI tract;desufflate a portion of the GI tract; deliver an injectate (e.g. intotissue and/or onto the surface of tissue); deliver a tissue expandingfluid (e.g. into tissue); steer the distal portion of a shaft; translatea control cable or control rod (hereinafter “control rod”); activate asensor (e.g. record a signal); activate a transducer; and combinationsof one or more of these. In some embodiments, handles 102, 22, 32 and/or42 can comprise a user interface configured to control one or morecomponents of system 10, such as controls 104, 24, 34 and/or 44,respectively, each of which can be constructed and arranged to controloperation of one or more of: catheter 100, catheter 20, catheter 30,catheter 40 and/or console 200. In some embodiments, controls 104, 24,34 and/or 44 can comprise one or more user input and/or user outputcomponents, such as a component selected from the group consisting of:screen; touchscreen; light; audible transducer such as a beeper orspeaker; tactical transducer such as a vibratory motor assembly; akeyboard; a membrane keypad; a switch; a safety-switch 206 such as afoot-activated switch; a mouse; a microphone; and combinations of one ormore of these.

Handles 102, 22, 32 and 42 each attach to the proximal end of shafts110, 21, 31 and 41, respectively. Shafts 110, 21, 31 and 41 eachtypically comprise a relatively flexible shaft comprising one or moreinternal lumens or other passageways. Shafts 110, 21, 31 and/or 41 cancomprise a lumen, such as lumen 116 of shaft 110 shown, that is sizedand configured to perform a function selected from the group consistingof: provide for the delivery or extraction of one or more fluids such asablation fluids, cooling fluids, insufflation fluids, pneumatic fluids,hydraulic fluids and/or balloon expanding fluids; allow over theguidewire delivery of the associated device; surround an electrical wireproviding electrical energy and/or signals; slidingly receive a controlshaft or other control filament such as a control filament used toexpand or contract a functional assembly (e.g. functional assembly 130)or otherwise modify the shape of a portion of the device; andcombinations of one or more of these. Shafts 110, 21, 31 and/or 41 cancomprise a braided or otherwise reinforced shaft or they can include oneor more portions which are reinforced. Shafts 110, 21, 31 and/or 41 cancomprise a multi-layer construction, such as a construction including abraid, a friction-reduced (e.g. PTFE) liner, a thermally insulatinglayer and/or an electrically insulating layer. Shafts 110, 21, 31 and/or41 can include a bulbous distal end, such as bulbous end 115 of shaft110 shown, a circular or elliptical shaped enlarged end configured toimprove traversing the innermost tissue of the duodenum or other luminaltissue of the GI tract (e.g. to smoothly advance within a lumen whosewalls include villi and/or one or more folds). As described hereabove,shafts 110, 21, 31 and/or 41 can include a guidewire lumen, such aslumen 116 of shaft 110.

Positioned on the distal end or on a distal portion of shafts 110, 21,31 and 41 is an expandable functional assembly, functional assemblies130, 25, 35 and 45, respectively. Functional assemblies 130, 25, 35 and45 are each constructed and arranged to be radially expanded andsubsequently radially compacted (each shown in their radially expandedstate in FIG. 2), one or more times during use. Each of functionalassemblies 130, 25, 35 and 45 can include an expandable element selectedfrom the group consisting of: an inflatable balloon; a radiallyexpandable cage or stent; one or more radially deployable arms; anexpandable helix; an unfurlable compacted coiled structure; anunfurlable sheet; an unfoldable compacted structure; and combinations ofone or more of these. Functional assembly 130 can comprise a functionalelement, such as treatment element 135 shown, configured to treat targettissue. Treatment element 135 can be similar to one or more functionalelements 139 described hereabove in reference to catheter 100 of FIG. 1.

In some embodiments, catheter 100, tissue expansion catheter 20, lumendiameter sizing catheter 30 and/or multi-function catheter 40, withtheir functional assemblies 130, 25, 35 and 45 (respectively) in theirradially compacted state, are sized and configured to be insertedthrough a working channel of endoscope 50 a and/or sheath 80, afterendoscope 50 a and/or sheath 80 have been inserted into a patient (e.g.through the mouth and advanced such that their distal end resides in theduodenum or other GI tract location). In some embodiments, catheter 100,tissue expansion catheter 20, sizing catheter 30 and/or multi-functioncatheter 40 are sized and configured to be inserted through the mouthand into a patient's GI tract alongside endoscope 50 a. In someembodiments, catheter 100, tissue expansion catheter 20, lumen diametersizing catheter 30 and/or multi-function catheter 40 are sized andconfigured to be inserted into a patient over one or more guidewires 60.For insertion over a guidewire, the shafts 110, 21, 31 and/or 41 and thedistal portions of the associated catheter 100, 20, 30 and/or 40 cancomprise sufficient flexibility to traverse the pylorus and enter theduodenum, while having sufficient column and torsional strength to beadvanced through the duodenum. In some embodiments, one or more portionsof the shafts 110, 21, 31 and 41 have variable stiffness (e.g. stifferin a proximal portion of the shaft) and/or include a lumen configured toaccept a stiffening wire or other stiffening mandrel (e.g. a taperedmandrel), such as stiffening wire 67. Alternatively or additionally,stiffening wire 67 can be inserted into endoscope 50 a and/or sheath 80,such as to facilitate their advancement through the stomach and into theduodenum. In some embodiments, shaft 110 comprises at least a braidedportion. In some embodiments, shaft 110 comprises a tapered portion,such as is described herebelow in reference to FIG. 27.

Console 200 can be constructed and arranged in a similar fashion toconsole 200 of FIG. 1 described hereabove. Console 200 can comprise anoperator (e.g. clinician) accessible user interface 205. User interface205 can comprise one or more user output and/or user input components,such as a component selected from the group consisting of: screen;touchscreen; light; audible transducer such as a beeper or speaker;tactical transducer such as a vibratory motor assembly; a keyboard; amembrane keypad; a switch; safety-switch 206 such as a foot-activatedswitch; a mouse; a microphone; and combinations of one or more of these.

Console 200 can comprise a controller, such as controller 250.Controller 250 can comprise one or more components or assembliesselected from the group consisting of: an electronics module; a powersupply; memory (e.g. volatile or non-volatile memory circuitry); amicrocontroller; a microprocessor; a signal analyzer; an analog todigital converter; a digital to analog converter; a sensor interface;transducer drive circuitry; software; and combinations of one or more ofthese. Controller 250 can comprise one or more algorithms 251, which canbe constructed and arranged to automatically and/or manually controland/or monitor one or more devices, assemblies and/or components ofsystem 10. Algorithm 251 of controller 250 can be configured todetermine one or more tissue expansion and/or tissue treatmentparameters. In some embodiments, algorithm 251 processes one or moresensor signals (e.g. signals from functional elements 139, 29, 39 and/or49 described herebelow) to modify one or more of: volume of tissueexpansion fluid delivered; rate of tissue expansion fluid delivery;temperature of tissue expansion fluid delivery; amount of ablative fluiddelivered; rate of ablative fluid delivery; energy delivered; power ofenergy delivered; voltage of energy delivered; current of energydelivered; temperature of ablative fluid or energy delivered; deviceand/or treatment element location within the GI tract; functionalassembly pressure (e.g. balloon pressure); and combinations of one ormore of these. Treatment element 135 can deliver energy to a surface oftissue, a delivery zone as described hereabove, which is a subset of thetarget tissue treated by that energy delivery (e.g. due to theconduction of heat or other energy to neighboring tissue). Algorithm 251can comprise an algorithm configured to determine a delivery zoneparameter such as a delivery zone parameter selected from the groupconsisting of: anatomical location of a delivery zone; size of deliveryzone; percentage of delivery zone to receive energy; type of energy tobe delivered to a delivery zone; amount of energy to be delivered to adelivery zone; and combinations of one or more of these. Informationregarding the delivery zone parameter can be provided to an operator ofsystem 10 (e.g. a clinician), such as via user interface 205. Thisinformation can be employed to set a delivery zone parameter, assist theoperator in determining the completion status of the procedure (e.g.determining when the procedure is sufficiently complete) and/or toadvise the operator to continue to complete a pre-specified area orvolume of target tissue. The total area of treatment or number ofdelivery zones or number of treatments during a particular procedure(any of which can be employed in algorithm 251) can be defined byclinical and/or demographic data of the patient.

Console 200 can comprise one or more reservoirs or other sources offluid, such as reservoir 220. Reservoir 220 can be configured to providefluid at an ablative temperature (e.g. sufficiently hot or cold toablate tissue), a treatment neutralizing (e.g. warming or cooling) fluidconfigured to reduce ablative effects, an insufflation fluid, injectate221 (e.g. similar to injectate 221 described hereabove in reference toFIG. 1), an agent (e.g. agent 420 described hereabove in reference toFIG. 1), and/or another fluid. Console 200 can comprise an energydelivery unit, such as EDU 260, configured to deliver energy totreatment element 135 and/or one or more other components of system 10,such as one or more components of devices 100, 20, 30 and/or 40.Controller 250, reservoir 220 and/or EDU 260 can be of similarconstruction and arrangement as controller 250, reservoir 220 and/or EDU260, respectively, of FIG. 1 described hereabove.

Console 200 can comprise a pressure or other fluid pumping assembly,such as pumping assembly 225 constructed and arranged to deliverpositive pressure or vacuum pressure (e.g. any pressure below anotherpressure) to one or more fluid delivery elements or fluid pathways (e.g.lumens) of system 10. Pumping assembly 225 can be constructed andarranged to provide and/or extract fluid to radially expand and/orradially compact, respectively, one or more expandable assemblies, suchas functional assemblies 130, 25, 35 and/or 45. Pumping assembly 225 cancomprise one or more pumps or other fluid delivery mechanisms, and/orother pressure or vacuum generators. In some embodiments, pumpingassembly 225 is constructed and arranged to provide a recirculatingablative fluid (e.g. hot or cold) to catheter 100 and/or catheter 40. Inthese embodiments, pumping assembly 225 can be constructed and arrangedto further provide a recirculating “neutralizing fluid” (e.g. a coolingor warming fluid, respectively, to counteract the ablative effects ofthe previously circulated ablative fluid) to balloon 36 and/or 46,respectively. Pumping assembly 225 can be of similar construction andarrangement as pumping assembly 225 of FIG. 1 described hereabove. Insome embodiments, pumping assembly 225 is constructed and arranged todeliver injectate 221 to a functional assembly 130, 25, 35 and/or 45,such as an injectate configured to expand tissue and/or to create atherapeutic restriction, as described herein, such as an injectatesimilar to injectate 221 described hereabove in reference to FIG. 1.

Console 200 includes port 203, which is operably attached to one or moreof: user interface 205 (e.g. safety-switch 206 or another component ofuser interface 205), controller 250, reservoir 220 and/or pumpingassembly 225. Port 203 is constructed and arranged to operably attach(e.g. fluidly, electrically, optically, acoustically, mechanicallyand/or otherwise operably attach) to one or more of ports 103, 23, 33and 43 of devices 100, 20, 30 and 40, respectively. Console 200 can beconstructed and arranged to deliver fluids and/or energy via port 203 toone or more of devices 100, 20, 30 and 40. In some embodiments, aninflation fluid and/or a fluid at an ablative temperature is providedand/or recovered by console 200, such as a fluid at an ablativetemperature delivered to functional assembly 130 of catheter 100 and/orfunctional assembly 45 of catheter 40. In some embodiments,insufflation, pneumatic and/or hydraulic fluids are delivered and/orrecovered by console 200 via port 203. In some embodiments, an injectate221 is delivered by console 200, such as is described herebelow inreference to tissue expansion catheter 20 and multi-function catheter40. In some embodiments, one or more control rods (not shown) aretranslated (e.g. advanced and/or retracted) within one or more lumens orother openings of catheter 100, 20, 30 and/or 40, such as to expand acage, deploy a radially deployable arm, change the shape of an assembly,translate an assembly, rotate an assembly and/or otherwise control theposition, shape and/or configuration of an assembly of system 10.

Console 200 can provide energy to, send information to and/or recordand/or receive a signal from one or more other elements of catheter 100,such as functional elements 139, 29, 39 and/or 49 described herebelow.

Catheter 100 can be constructed and arranged to treat target tissue of apatient. In some embodiments, catheter 100 is of similar constructionand arrangement as catheter 100 of FIG. 1 described hereabove. Catheter100 comprises handle 102 which attaches to a proximal end of shaft 110and includes port 103 for operable attachment to console 200. Positionedon the distal end or on a distal portion of shaft 110 is functionalassembly 130. Functional assembly 130 can comprise an expandable elementselected from the group consisting of: an inflatable balloon such asballoon 136 shown; a radially expandable cage or stent; one or moreradially deployable arms; an expandable helix; an unfurlable compactedcoiled structure; an unfurlable sheet; an unfoldable compactedstructure; and combinations of one or more of these. Functional assembly130 can comprise an energy delivery element or other tissue treatmentelement 135, such as an energy delivery element configured to deliverthermal, electrical, light, sound and/or ablative chemical energy totarget tissue. In some embodiments, treatment element 135 comprises amechanical abrader configured to treat tissue through abrasion. In someembodiments, functional assembly 130 comprises a balloon 136 which canbe configured to receive one or more expansion and/or ablative fluids.Balloon 136 can comprise a compliant balloon, a non-compliant balloon, apressure-thresholded balloon and/or otherwise be constructed andarranged as described in detail hereabove. Functional assembly 130 canbe configured to both ablate (e.g. via a hot or cold ablative fluid) andneutralize the ablation (e.g. via a cooling or warming fluid,respectively), prior to and/or after the ablation, as described herein.

Via port 103, console 200 can provide and/or extract one or more fluidsto and/or from one or more lumens or other flow pathways of catheter100, such as fluid provided by reservoir 220 and/or propelled by (i.e.delivered and/or extracted by) pumping assembly 225. Console 200, viaEDU 260, can be configured to provide energy to one or more treatmentelements 135 of catheter 100, such as energy contained in fluid at anablative temperature (hot and/or cold), electrical energy (e.g. RF ormicrowave energy), light energy (e.g. laser light energy), or soundenergy (e.g. subsonic or ultrasonic sound energy). In some embodiments,console 200 provides a fluid configured to treat target tissue withdirect contact, such as an ablating agent (e.g. a sclerosant or otherchemically ablative agent) and/or a fluid at an ablative temperature,either or both delivered directly to a target tissue surface.

In some embodiments, treatment element 135 comprises a fluid at anablative temperature provided by console 200. In these embodiments,treatment element 135 can comprise a sufficiently hot fluid that isintroduced into balloon 136 for a first time period to ablate targettissue, after which a cooling fluid is introduced into balloon 136, fora second time period, to extract heat from tissue (e.g. extract heatfrom target tissue and/or non-target tissue to reduce the ablationeffect). Alternatively or additionally, a cooling fluid can beintroduced into balloon 136 prior to the delivery of the hot fluid (e.g.for a third time period). In some embodiments, treatment element 135comprises a sufficiently cold fluid that is introduced into balloon 136for a first time period to ablate target tissue, after which a highertemperature fluid is introduced into balloon 136, for a second timeperiod, to warm tissue (e.g. warm target tissue and/or non-target tissueto reduce the ablation effect). Alternatively or additionally, a warmingfluid can be introduced into balloon 136 prior to the delivery of thecold fluid (e.g. for a third time period). Both the ablative andablation-reducing fluids can be provided by console 200. These fluidscan be provided in a recirculating manner as described in applicant'sco-pending application U.S. patent application Ser. No. 14/470,503,entitled “Heat Ablation Systems, Devices and Methods for the Treatmentof Tissue”, filed Aug. 27, 2014, the content of which is incorporatedherein by reference in its entirety for all purposes. Alternatively oradditionally, these fluids can be provided in a single bolus manner asdescribed in applicant's co-pending U.S. patent application Ser. No.14/917,243, entitled “Systems, Method and Devices for Treatment ofTarget Tissue”, filed Mar. 7, 2016, the content of which is incorporatedherein by reference in its entirety for all purposes. In someembodiments, thermal ablation is performed using system 10 as describedherein.

In some embodiments, target tissue and/or tissue proximate the targettissue is cooled, heated and subsequently cooled again. In theseembodiments, target tissue and/or tissue proximate the target tissue canbe cooled during at least a portion of a first step, such as a firststep including supplying a first fluid (e.g. a recirculating fluid) tofunctional assembly 130 for a first time period (e.g. a duration of atleast 10 seconds or approximately between 15-30 seconds), wherein thefirst fluid is supplied at a cooling temperature (e.g. continuouslysupplied by reservoir 220 at a temperature of approximately 10° C.-25°C.). In a subsequent second step, target tissue and/or tissue proximatethe target tissue can be heated (e.g. ablated) during at least a portionof the second step, such as a second step including supplying a secondfluid (e.g. a recirculating fluid) to functional assembly 130 for asecond time period (e.g. a duration of at least 5 seconds orapproximately between 8-15 seconds), wherein the second fluid issupplied at a heat ablating temperature (e.g. continuously supplied byreservoir 220 at a temperature of approximately 85° C.-95° C.). In asubsequent third step, target tissue and/or tissue proximate the targettissue can be cooled during at least a portion of the third step, suchas a third step including supplying a third fluid (e.g. a recirculatingfluid) to functional assembly 130 for a third time period (e.g. aduration of at least 10 seconds or approximately between 15-30 seconds),wherein the second fluid is supplied at a cooling temperature (e.g.continuously supplied by reservoir 220 at a temperature of approximately10° C.-25° C.). In some embodiments, other temperatures and/or durationsfor each heating or cooling cycle are used. In some embodiments, thesecond time period in which a hot fluid is supplied to functionalassembly 130 comprises a time less than the first time period and/or thethird time period. In some embodiments, the temperature of the fluidsupplied to functional assembly 130 during the first time period and/orthe third time period is at least 18° C. less and/or at least 60° C.less than the temperature of the fluid supplied to functional assembly130 during the second time period. In some embodiments, the firsttemperature and the third temperature comprise a similar temperature. Insome embodiments, a cooling fluid at approximately 10° C. is deliveredto functional assembly 130 for approximately 30 seconds, after which anablative fluid at approximately 95° C. is delivered to functionalassembly 130 for approximately 12 seconds, after which a cooling fluidat approximately 10° C. is delivered to functional assembly 130 forapproximately 30 seconds. Alternatively, a warming fluid can bedelivered to functional assembly 130 prior to and/or after the deliveryof a cryogenically ablative fluid (e.g. for the similar time periods asdescribed herein in reference to heat ablation). In some embodiments,the volume, temperature and/or duration of fluid delivered to functionalassembly 130 is automatically and/or dynamically adjusted, such as anadjustment performed based on a signal provided by one or more sensorsas described herein. For example, a temperature and/or duration can beadjusted during a first ablation of an axial segment of intestine and/orduring a subsequent second ablation of the same or different axialsegment of intestine. In some embodiments, a pre-cooling and/orpost-cooling step is used to avoid the need for a tissue expansion step(e.g. tissue expansion proximate tissue to be ablated in a heat ablationstep). In other embodiments, a tissue expansion step is included.

In some embodiments, a first axial segment of tubular tissue is cooled(e.g. non-ablatively cooled), via functional assembly 130, for a firsttime period TP₁, and subsequently heat ablated for a second time periodTP₂. A first reservoir 220 _(A) includes the cooling fluid at atemperature T_(A), (e.g. fluid continuously maintained or at leastinitially provided at temperature T_(A)) and a second reservoir 220 _(B)includes the (heat) ablative fluid at a temperature T_(B) (e.g. fluidcontinuously maintained or at least initially provided at temperatureT_(B)). In some embodiments, after the heat ablation during time periodTP₂, an additional tissue cooling step is performed via functionalassembly 130, for a third time period TP₃. Additionally axial segmentsof tubular tissue can subsequently be treated (e.g. additional axialsegments treated via tissue cooling and subsequent heat ablation, withor without a subsequent tissue cooling step). T_(A) can comprise atemperature at or below approximately 25° C., such as a temperature ator below approximately 20° C. and/or 15° C., and T_(B) can comprise atemperature at or above approximately 65° C., such as a temperature ator above approximately 75° C., 85° C. and/or 95° C. TP₁ can comprise atime duration of between 3 seconds and 60 seconds (e.g. between 20seconds and 40 seconds); TP₂ can comprise a time duration of between 1seconds and 30 seconds (e.g. between 5 seconds and 15 seconds); and TP₃can comprise a time duration of between 3 seconds and 60 seconds (e.g.between 20 seconds and 40 seconds). In these embodiments, T_(A), T_(B),TP₁, TP₂ and/or TP₃ can be varied (e.g. automatically by system 10),based on information recorded by a sensor of the present inventiveconcepts (e.g. a sensor measuring temperature, pressure, flow rateand/or other parameter at one or more locations of catheter 100, console200 or other component of system 10). One or more of T_(A), T_(B), TP₁,TP₂ and/or TP₃ can be held relatively constant or unchanged, during oneor more axial tissue segment ablations. However, one or more of T_(A),T_(B), TP₁, TP₂ and/or TP₃ can vary (e.g. be allowed to vary), such aswhen T_(A) increases during an extraction of cooling fluid from catheter100 (e.g. the recovered fluid warms the cooling fluid in the firstreservoir 220 _(A)). These variations (e.g. as measured by one or moresensors of system 10) can result in an adjustment (e.g. an automaticadjustment) to another parameter (e.g. T_(A), T_(B), TP₁, TP₂ and/orTP₃), such as an adjustment made by algorithm 251 (e.g. an algorithmcomprising a lookup table including reservoir temperatures andcorresponding treatment durations) based on a signal produced by one ormore functional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.In some embodiments, T_(A), T_(B) TP₁, TP₂ and/or TP₃ are varied basedon the value of T_(A) and/or T_(B). For example, if the temperatureT_(A) of the cooling fluid were to increase during a multi-ablationprocedure, the time period TP₂ and/or temperature T_(B) could becompensatingly adjusted (e.g. decreased). In some embodiments, timeperiod TP₂ is decreased by up to 2 seconds (e.g. from an initial timeperiod of approximately 11 to 13 seconds, in one or more decrements), asthe temperature T_(A) increases by up to 16° C. (e.g. from a startingtemperature of approximately 9° C.), such as during an clinicalprocedure comprising ablation of two or more axial segments (e.g.ablation of between two and six axial segments). While the previousembodiments have been described in reference to a cooling of tissuefollowed by a heat ablation of tissue (which may also include asubsequent tissue cooling step), alternatively, system 10 can beconfigured to (non-ablatively) warm tissue, followed by cryogenicablation of tissue (which can also include a subsequent tissue warmingstep).

In some embodiments, treatment element 135 comprises one or more energyor other tissue treatment elements positioned in, on and/or withinfunctional assembly 130. Treatment element 135 can comprise one or moreenergy delivery elements configured to deliver energy to target tissue,such as an energy delivery element selected from the group consistingof: a fixed or recirculating volume of fluid at a high enoughtemperature to ablate tissue; a fixed or recirculating volume of fluidat a low enough temperature to ablate tissue; one or more thermal energydelivery elements such as one or more elements configured to deliverheat energy or cryogenic energy; an array of electrodes such as an arrayof electrodes configured to deliver radiofrequency (RF) energy; one ormore electromagnetic energy delivery elements such as one or moreelements configured to deliver microwave energy; one or more opticalelements configured to deliver light energy such as laser light energy;one or more sound energy delivery elements such as one or more elementsconfigured to deliver subsonic and/or ultrasonic sound energy; one ormore chemical or other agent delivery elements; and combinations of oneor more of these. In some embodiments, catheter 100 is constructed andarranged to deliver RF energy, such as is described in applicant'sco-pending U.S. patent application Ser. No. 14/609,332, entitled“Electrical Energy Ablation Systems, Devices and Methods for theTreatment of Tissue”, filed Jan. 29, 2015; and/or to deliver ablativefluid directly to tissue, such as is described in applicant's co-pendingU.S. patent application Ser. No. 14/609,334, entitled “Ablation Systems,Devices and Methods for the Treatment of Tissue”, filed Jan. 29, 2015;the content of each of which is incorporated herein by reference in itsentirety for all purposes.

In some embodiments, catheter 100 is further constructed and arranged toprovide geometric information (e g diameter information) of a luminalstructure such as the duodenum. In these embodiments, catheter 100 andfunctional assembly 130 can be of similar construction and arrangementas functional assembly 35 and lumen diameter sizing catheter 30described herebelow.

In some embodiments, system 10 comprises one or more devices forexpanding target tissue or tissue proximate target tissue, such astissue expansion catheter 20. In some embodiments, target tissue to betreated comprises mucosal tissue and the tissue to be expanded comprisessubmucosal tissue proximate the mucosal tissue to be treated. In someembodiments, tissue expansion catheter 20 is of similar construction andarrangement as catheter 100 described hereabove in reference to FIG. 1.In some embodiments, tissue expansion catheter 20 is of similarconstruction and arrangement as a tissue expansion device described inapplicant's co-pending International PCT Patent Application SerialNumber PCT/US2015/022293, entitled “Injectate Delivery Devices, Systemsand Methods”, filed Mar. 24, 2015, the content of which is incorporatedherein by reference in its entirety for all purposes. Tissue expansioncatheter 20 can be configured to expand a full or partialcircumferential segment of luminal wall tissue, such as to expand one ormore layers of submucosal tissue in one or more axial segments of theduodenum or other portion of the GI tract. Tissue expansion catheter 20can be configured to expand multiple segments of GI tract tissue, suchas multiple relatively contiguous segments of submucosal tissue expandedas described in detail herein.

Tissue expansion catheter 20 comprises handle 22 which attaches to aproximal end of shaft 21 and includes port 23 for operable attachment toconsole 200. Positioned on the distal end of shaft 21 or on a distalportion of catheter 20 is functional assembly 25. Functional assembly 25can comprise an expandable element selected from the group consistingof: an inflatable balloon such as balloon 26 shown; a radiallyexpandable cage or stent; one or more radially deployable arms; anexpandable helix; an unfurlable compacted coiled structure; anunfurlable sheet; an unfoldable compacted structure; and combinations ofone or more of these. Balloon 26 can comprise a compliant balloon, anon-compliant balloon, a pressure-thresholded balloon and/or otherwiseit can be constructed and arranged as described in detail hereabove.Balloon 26 can comprise a tissue-contacting length of between 20 mm and26 mm, such as a tissue-contacting length of approximately 23 mm Balloon26 can comprise a wall thickness of between 0.0002″ and 0.0010″, such asa wall thickness of approximately 0.0005″. Functional assembly 25 can beconfigured to expand to a diameter between 27.5 mm and 37.5 mm, such asa diameter of approximately 32.5 mm Functional assembly 25 can beconfigured to be expanded via control 24 and/or via user interface 205of console 200 (e.g. inflated and deflated by delivery and extraction,respectively, of air, water and/or other fluids by console 200).

Functional assembly 25 comprises one or more fluid delivery elements 28.The one or more fluid delivery elements 28 can each comprise an elementselected from the group consisting of: needle such as a straight needleor a curved needle; nozzle; fluid jet; iontophoretic fluid deliveryelement; and combinations of one or more of these. The one or more fluiddelivery elements 28 are configured to deliver injectate 221 and/oranother fluid to tissue when functional assembly 25 is expanded (e.g. atleast partially expanded with inflation fluid provided by console 200),positioning the fluid delivery elements 28 proximate (e.g. in contactwith or close to) tissue to be expanded, such as luminal wall tissue ofthe GI tract.

The one or more fluid delivery elements 28 can be configured to beadvanced (e.g. advanced into tissue) and retracted via control 24 ofcatheter 20. The one or more fluid delivery elements 28 can bepositioned in one or more ports 27, as shown in FIG. 2. In someembodiments, a vacuum provided by console 200 causes tissue to tendtoward and/or enter each port 27, such that each fluid delivery element28 can inject fluid (e.g. injectate 221) into the engaged and/orcaptured tissue without having to extend significantly beyond theassociated port 27 (e.g. fluid delivery element 28 can be configured toremain within port 27 during delivery of fluid into tissue capturedwithin port 27). By limiting excursion of fluid delivery element 28 outof port 27, risk of fluid delivery element 28 and/or injectate 221penetrating through the outer surface of the GI tract is prevented or atleast significantly reduced. In some embodiments, fluid can be deliveredinto tissue by fluid delivery element 28 with or without advancement offluid delivery element 28 into the captured tissue (e.g. tissue is drawninto a port 27 via an applied vacuum such that fluid delivery element 28penetrates or otherwise engages the tissue for fluid delivery withoutadvancement of the fluid delivery element 28). In some embodiments,fluid delivery elements 28, ports 27 and/or other portions of tissueexpansion catheter 20 are of similar construction and arrangement as atissue expansion device described in applicant's co-pendingInternational PCT Patent Application Serial Number PCT/US2015/022293,entitled “Injectate Delivery Devices, Systems and Methods”, filed Mar.24, 2015, the content of which is incorporated herein by reference inits entirety for all purposes.

In some embodiments, functional assembly 25 comprises three or morefluid delivery elements 28 arranged in a circumferential pattern, suchas three fluid delivery elements 28 arranged along a circumference andseparated by approximately 120°. The multiple fluid delivery elements 28can be configured to be advanced individually (e.g. via multiplecontrols 24), or simultaneously (e.g. via a single control 24). In someembodiments, two fluid delivery elements 28 are separated byapproximately 180°. In some embodiments, four fluid delivery elements 28are separated by approximately 90°.

In some embodiments, system 10 includes injectate 221 which can beprovided by console 200 to catheter 20, and delivered into tissue by theone or more fluid delivery elements 28. Injectate 221 can comprise oneor more materials as described hereabove in reference to injectate 221of FIG. 1.

In some embodiments, catheter 20 and/or console 200 are configured toreduce a volume of fluid (e.g. liquid or gas) within functional assembly25 (e.g. within balloon 26) as injectate 221 is delivered into tissue(e.g. submucosal tissue), such as to prevent excessive force beingapplied by functional assembly 25 to tissue proximate the expandingtissue (i.e. due to the decreasing luminal diameter proximate theexpanding tissue in contact with functional assembly 25). In someembodiments, system 10 is constructed and arranged to inflate orotherwise expand functional assembly 25 (e.g. balloon 26) to a firsttarget pressure, such as a pressure of approximately 0.7 psi. Injectate221 is delivered via one or more fluid delivery elements 28 intosubmucosal tissue (e.g. simultaneously or sequentially). Fluid containedwithin functional assembly 25 (e.g. within balloon 26) can be reduced orincreased to maintain the pressure at a second target pressure, forexample a pressure higher than the first target pressure such as apressure between 0.8 psi and 0.9 psi. Fluid of up to 10 ml can beinjected while maintaining the second target pressure in functionalassembly 25 (e.g. by decreasing the amount of fluid in functionalassembly 25 to cause 1 mm steps of diameter decrease of functionalassembly 25).

In some embodiments, tissue expansion catheter 20 is further constructedand arranged to provide geometric information (e g diameter information)of a luminal structure such as the duodenum or other intestinallocation. In these embodiments, catheter 20 and functional assembly 25can be of similar construction and arrangement as lumen diameter sizingcatheter 30 and functional assembly 35, respectively, describedherebelow.

In some embodiments, system 10 comprises one or more separate devicesfor estimating or otherwise measuring (e.g. “sizing”) the diameter,average diameter, equivalent diameter, minimum diameter, cross sectionalarea and/or other geometric measure (herein “diameter”) of luminaltissue, such as lumen diameter sizing catheter 30. Sizing catheter 30 isconstructed and arranged to be placed into one or more locations of theGI tract or other internal location of the patient and measure thediameter or other geometric parameter of tissue. In some embodiments,sizing catheter 30 is of similar construction and arrangement ascatheter 100 described hereabove in reference to FIG. 1. Sizing catheter30 can be configured to measure the diameter of multiple segments ofintestinal or other GI tract tissue, such as to measure multiplediameters along the length of the duodenum.

Catheter 30 comprises handle 32 which attaches to a proximal end ofshaft 31 and includes port 33 for operable attachment to console 200.Positioned on the distal end of shaft 31 or on a distal portion ofcatheter 30 is functional assembly 35. Functional assembly 35 cancomprise an expandable cage, balloon 36, or other expandable element asdescribed herein, constructed and arranged to measure the inner surfacediameter of tubular tissue (e.g. average diameter, equivalent diameter,minimum diameter, cross sectional area and/or other geometric measure ofthe inner surface of tubular tissue), such as a diameter of the duodenumor jejunum. Balloon 36 can comprise a compliant balloon, a non-compliantballoon, a pressure-thresholded balloon and/or otherwise be constructedand arranged as described in detail hereabove. Functional assembly 35can be configured to be expanded via control 34 and/or via userinterface 205 of console 200 (e.g. inflated and deflated by delivery andextraction, respectively, of fluids by console 200).

Fluids delivered by console 200 to functional assembly 35 (e.g. fluidssupplied by reservoir 220) can be provided at one or more predeterminedpressures, or pressure profiles. Diameter measurements can beaccomplished by performing a visualization procedure (manual orautomated) that assesses functional assembly 35 diameter. Alternativelyor additionally, functional assembly 35 can be controllably filled witha fluid, and controller 250 can include an algorithm (e.g. algorithm 251described hereabove in reference to FIG. 1) that correlates the fluidvolume and/or fluid pressure to the diameter of tubular tissue incontact with functional assembly 35. In some embodiments, subsequentselection (e.g. device model or size selection) and/or expansiondiameter (e.g. inflated diameter chosen for sufficient apposition) offunctional assemblies 130, 25 and/or 45 of devices 100, 20 and/or 40,respectively, can be determined using the information provided by sizingcatheter 30 and/or console 200. In some embodiments, catheter 30performs one or more sizing procedures as described herein.

In some embodiments, functional assembly 35 comprises a balloon,expandable cage and/or other expandable element that includes two ormore electrodes configured to provide a tissue impedance measurementwhose value can be correlated to a level of apposition of functionalassembly 35, and whose expanded diameter (e.g. visually or otherwisemeasured) correlates to a diameter of tubular tissue in contact with theexpandable element. Alternatively or additionally, functional assembly130 of catheter 100, functional assembly 25 of catheter 20 and/orfunctional assembly 45 of catheter 40 can be used to measure a diameterof the inner surface of tubular tissue, such as has been describedhereabove in reference to functional assembly 35 and catheter 30.

In some embodiments, system 10 comprises one or more devices, such asmulti-function catheter 40 shown, that are constructed and arranged toperform two or more functions selected from the group consisting of:treat target tissue such as to deliver energy or otherwise ablate targettissue; expand tissue such as to expand one or more layers of submucosaltissue (e.g. proximate to and/or including target tissue); and determineor estimate a diameter (e.g. an average diameter, equivalent diameter,minimum diameter, cross sectional area and/or other geometric measure)of a lumen of tubular tissue; and combinations of one or more of these.Multi-function catheter 40 is constructed and arranged to be placed intoone or more locations of the GI tract or other internal location of thepatient and perform two or more of the functions listed above. In someembodiments, multi-function catheter 40 is of similar construction andarrangement as catheter 100 described hereabove in reference to FIG. 1.Multi-function catheter 40 can be configured to perform the multiplefunctions at multiple segments of GI tract, such as multiple relativelycontiguous axial segments of the duodenum or other intestinal locationas is described herein.

Catheter 40 comprises handle 42 which attaches to a proximal end ofshaft 41 and includes port 43 for operable attachment to console 200.Positioned on the distal end of shaft 41 or on a distal portion ofcatheter 40 is functional assembly 45. Functional assembly 45 cancomprise an expandable cage, balloon 46, or other expandable elementconstructed and arranged to be positioned in apposition with and/or inclose proximity to the inner wall of tubular tissue, such as tissue ofthe duodenum, jejunum and/or other intestinal location. Balloon 46 cancomprise a compliant balloon, a non-compliant balloon, apressure-thresholded balloon and/or otherwise be constructed andarranged as described in detail hereabove. Functional assembly 45 can beconfigured to be expanded via control 44 and/or via user interface 205of console 200 (e.g. inflated and deflated by delivery and extraction,respectively, of fluids by console 200).

Functional assembly 45 can comprise treatment element 135′, which cancomprise a fluid at an ablative temperature delivered into functionalassembly 45 by console 200 and/or an energy delivery element permanentlypositioned on, in and/or within functional assembly 45 (e.g. an energydelivery element configured to deliver thermal energy, electricalenergy, light energy, sound energy and/or chemical energy as describedherein). In some embodiments, treatment element 135′ comprises amechanical abrader configured to treat tissue through abrasion. In someembodiments, treatment element 135′ is of similar construction andarrangement as functional element 139 a of catheter 100 of FIG. 1.Functional assembly 45 can be configured to both ablate (e.g. via a hotor cold ablative fluid) and neutralize (e.g. via a cooling or warmingfluid, respectively), prior to and/or after the ablation, as describedherein.

Alternatively or additionally, functional assembly 45 can comprise oneor more elements configured to expand tissue, such as fluid deliveryelements 48. Fluid delivery elements 48 can each be positioned withinone or more ports 47 as shown. Fluid delivery elements 48 and ports 47can be constructed and arranged as described hereabove in reference tofluid delivery element 139 c and ports 137, respectively, of catheter100 of FIG. 1.

Devices 100, 20, 30 and/or 40 can comprise one or more functionalelements, such as functional elements 139, 29, 39 and/or 49,respectively, shown positioned in, on and/or within functionalassemblies 130, 25, 35 and 45, respectively. Alternatively oradditionally, one or more functional elements 139, 29, 39 and/or 49 canbe located at a different location of the associated device, such as in,on and/or within the associated shaft and/or handle of the device. Insome embodiments, one or more functional elements 139, 29, 39 and/or 49comprise a sensor, such as a sensor selected from the group consistingof: physiologic sensor; blood glucose sensor; blood gas sensor; bloodsensor; respiration sensor; EKG sensor; EEG sensor; neuronal activitysensor; blood pressure sensor; flow sensor such as a flow rate sensor;volume sensor; pressure sensor; force sensor; sound sensor such as anultrasound sensor; electromagnetic sensor such as an electromagneticfield sensor or an electrode; gas bubble detector such as an ultrasonicgas bubble detector; strain gauge; magnetic sensor; ultrasonic sensor;optical sensor such as a light sensor; chemical sensor; visual sensorsuch as a camera; temperature sensor such as a thermocouple, thermistor,resistance temperature detector or optical temperature sensor; impedancesensor such as a tissue impedance sensor; and combinations of one ormore of these. Alternatively or additionally, one or more functionalelements 139, 29, 39 and/or 49 comprise a transducer, such as atransducer selected from the group consisting of: an energy convertingtransducer; a heating element; a cooling element such as a Peltiercooling element; a drug delivery element such as an iontophoretic drugdelivery element; a magnetic transducer; a magnetic field generator; anultrasound wave generator such as a piezo crystal; a light producingelement such as a visible and/or infrared light emitting diode; a motor;a pressure transducer; a vibrational transducer; a solenoid; a fluidagitating element; and combinations of one or more of these. Functionalelements 139, 29, 39 and/or 49 can be electrically connected to EDU 260(e.g. to receive power, send signals and/or receive signals), such asvia an electrical connection provided by port 203. Functional elements139, 29, 39 and/or 49 can send or receive signals from controller 250 ofconsole 200, such as one or more sensor signals used to control ablationenergy provided by console 200. Functional elements 139, 29, 39 and/or49 can be activated and/or otherwise controlled via controls 104, 24, 34and/or 44, respectively. Alternatively or additionally, user interface205 of console 200 can be configured to allow operator control offunctional elements 139, 29, 39 and/or 49.

In some embodiments, console 200 comprises one or more functionalelements 209, comprising a sensor or transducer as described hereabove.Functional element 209 can comprise one or more pressure sensors, suchas one or more pressure sensors configured to provide a signal used toregulate fluid delivery provided to one or more of devices 100, 20, 30and/or 40. Functional element 209 can comprise one or more temperaturesensors, such as one or more temperature sensors that provide a signalused to regulate temperature of one or more fluids of console 200.Functional element 209 can be positioned to measure a parameter (e.g.temperature or pressure) of fluid within reservoir 220, within pumpingassembly 225 and/or within a fluid conduit of console 200.

In some embodiments, system 10 comprises one or more agents configuredto be delivered to the patient, such as agent 420. Agent 420 can bedelivered by one or more of devices 100, 20, 30, 40 and/or 50, or by aseparate device such as a syringe or other medication delivery device.In some embodiments, injectate 221 comprises agent 420, such as whenagent 420 is delivered by one or more fluid delivery elements 139 c asdescribed herein. In some embodiments, agent 420 comprises ananti-peristaltic agent, such as L-menthol (i.e. oil of peppermint)Alternatively or additionally, agent 420 can comprise glucagon,buscopan, hycosine, somatostatin, an opiod agent and/or anyanti-peristaltic agent. Agent 420 can be delivered into the GI tract,such as via endoscope 50 a, sheath 80 and/or devices 100, 20, 30 and/or40. Agent 420 can be delivered systemically, such as via an intravenousor intra-arterial access line, or injected directly into tissue. Agent420 can comprise a drug or other agent as described hereabove inreference to agent 420 of FIG. 1.

As described above, user interface 205 can comprise safety-switch 206such as a foot-activated switch. Safety-switch 206 can be configured toallow a clinician to activate or modify one or more processes of system10 without having to use his or her hands (e.g. without having to use adigit of the hand). In some embodiments, system 10 is constructed andarranged to perform a function selected from the group consisting of:automatic contraction (e.g. deflation) of functional assembly 130 ifsafety-switch 206 is not activated (e.g. continuously orsemi-continuously pushed, pressed or otherwise activated, such as by afoot or digit of an operator); automatic replacement of ablative fluid(e.g. hot fluid) with neutralizing fluid (e.g. cold fluid) ifsafety-switch 206 is not activated; initiate introduction of ablativefluid (e.g. hot fluid) into functional assembly 130 by activation ofsafety-switch 206 (e.g. after functional assembly 130 has beenpre-expanded with cold fluid and an operator has confirmed properposition for treatment); allow hands-free activation (e.g. initiation)of a treatment step such that one or more operators can maintain theirhands on one or more of endoscope 50 a and/or devices 100, 20, 30 and/or40; allow hands-free activation (e.g. initiation) of a treatment stepsuch that the required number of operators is reduced; and combinationsof one or more of these.

Each of devices 100, 20, 30 and/or 40 can be provided in one or moresizes, such as one or more lengths of the associated shaft 110, 21, 31and/or 41, respectively, and/or one or more diameters (e.g. expandeddiameter) of the associated functional assembly 130, 25, 35 and/or 45,respectively. Luminal sizing as described herein or other anatomicalinformation can be used to select the appropriately sized device totreat the patient.

In some embodiments, system 10 of FIG. 2 comprises one or more sensors,such as one or more functional elements 109, 119, 139, 209, 229 and/or309 described hereabove in reference to FIG. 1, that comprise a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts.

Applicant has conducted human studies with the systems, methods anddevices of the present inventive concepts. Included below are results ofearly human clinical studies conducted by the applicant, and associateddata collected.

Some patients received treatment of approximately 9 cm of relativelyfull-circumferential axial length of duodenal mucosa (via threeapproximately 3 cm hot fluid balloon-based ablations), and some patientsreceived treatment of less than or equal to 6 cm of relativelyfull-circumferential axial length of duodenal mucosa (via two or lessapproximately 3 cm hot fluid balloon-based ablations).

Early results showed: baseline HbA1c was 9.2% and FPG was 187 mg/dl. 1month post-procedure, HbA1c was reduced by 1.1% in LS-DMR patients(patients receiving duodenal mucosa treatments of approximately 9 cm(e.g. 9.3 cm) of duodenal tissue) but only 0.1% in SS-DMR patients(patients receiving duodenal mucosa treatment of approximately 3 cm(e.g. 3.4 cm) of duodenal tissue, the data representing 12 LS-DMRpatients vs 7 SS-DMR patients, each group at 1 month (p=0.058). By 3months, HbA1c was reduced by approximately 2% in LS-DMR patients but wasunchanged in SS-DMR patients (N=5 in each group at 3 months). FPGreductions in LS-DMR patients were −64 mg/dl and −67 mg/dl at 1 and 3months.

Table A below shows a breakdown of a number of patients who receivedvarious quantities of duodenal axial segment treatments comprisingdelivery of heat from an ablative fluid delivered to a balloon-basedtreatment assembly. Thirty five patients were treated in a dosimetricevaluation of the systems, methods and devices described herein. In thestudy, an ablation is defined as an axial length of circumferentiallyablated tissue, ablated with a single positioning of the balloon andsubsequent hot fluid delivery to the balloon. Ablation dose is definedas the total length of circumferentially ablated tissue on a singleprocedural day. A single patient received 5 ablations (the highest doseadministered), and duodenal stenosis presented as food intolerance andepigastric discomfort. After endoscopic balloon dilation, the patientrecovered without further issue. This patient with the duodenal stenosislost a substantial amount of weight in the 2 weeks after the developmentof stenosis (nearly 10 kilograms). Controlled duodenal stenosis may bean effective means of achieving substantial weight loss with itsattendant benefits on metabolic or obesity-related ailments. Creation ofa therapeutic restriction can be performed as described in co-pendingInternational Patent Application Serial Number PCT/US2014/066829, titled“Systems, Devices and Methods for the Creation of a TherapeuticRestriction in the Gastrointestinal Tract”, filed Nov. 21, 2014, thecontent of which is incorporated herein by reference in its entirety forall purposes.

TABLE A Number of Duodenal Number of Ablations Patients 0 2 1 6 2 4 3 224 0 5 1

In some embodiments, the systems, devices and methods of the presentinventive concepts can be configured to deliver at least two ablationsto target tissue (e.g. at least two sequential deliveries of energy orother treatments to different axial segments of GI mucosa), such as todeliver at least three ablations to target tissue. In some embodiments,a minimum and/or maximum amount of duodenal mucosa is treated, such ashas been described hereabove.

Table B is a table of cumulative demographic information for the first21 patients of the applicant's studies. These baseline characteristicsare generalizable and relevant to the Type 2 diabetes population.

TABLE B Characteristic Value (N = 32) N in calc Duaration diabetes - yr 5.1 +/− 2.9 27 Age - yr 52.9 +/− 7.6 26 Female sex - N (%) 12 (46.2) 26Weight - kg  86.7 +/− 13.2 26 Height - cm 165.7 +/− 10.2 26 BMI -kg/m{circumflex over ( )}2 31.6 +/− 4.0 26 BP Systolic - mmHg 122.5 +/−16.2 26 BP Diastolic - mmHg 77.2 +/− 8.0 26 Medications - N  1.7 +/− 0.619

In some embodiments, the systems, devices and methods of the presentinventive concepts can be configured to treat patients with acharacteristic selected from the group consisting of: duration ofdiabetes less than 10 years; age between 18 yrs and 75 yrs; BMI between20 and 60, such as a BMI between 24 and 40; and combinations thereof.

Table C is a table of results of applicant's studies, detailing recordeddose dependent improvements in glycemic control. Applicant measuredthree validated measures of glycemic control, Hemoglobin A1c (HbA1c),fasting plasma glucose (FPG), and two hour post-prandial glucose (2hPG).

TABLE C

In some embodiments, the systems, devices and methods of the presentinventive concepts can be configured to provide a therapeutic benefitselected from the group consisting of: a reduction in HbA1c of at least0.7%, 1.0% or 1.5% at three months, such as a reduction of approximately2.18 at three months; an FPG of no more than 150 mg/dl, 126 mg/dl or 100mg/dl, such as an FPG that can result with a reduction of approximately63.5 mg/dl; a 2hPG of no more than 250, 200 or 175, such as an 2hPG thatcan result with a reduction of approximately 103.7; and combinationsthereof.

In some embodiments, an absolute change of at least 0.7%, 1.0%, 1.5%and/or 2.0% in HbA1c is expected. In some embodiments, a relative changeabove an HbA1c target is expected, such as a relative change of at least50%, 75% or 100%, such as when the target HbA1c is an HbA1c ofapproximately 6.5%, 7.0% or 7.5%. It has been reported that a 1%absolute change in HbA1c correlates to a 40% reduction in risk ofmicrovascular complication due to diabetes.

FIG. 44 is a graph illustrating an approximately 2% HbA1c reduction inpatients receiving three or more ablations compared with no change inthose receiving fewer than 3 ablations.

In some embodiments, the systems, devices and methods of the presentinventive concepts can be configured to achieve an HbA1c level at orbelow 7.5%, or 7.0% or 6.5%, such as at a time period of 3 months ormore, such as by ablating a cumulative length of duodenal mucosa greaterthan 6 cm, greater than 7 cm, greater than 8 cm or greater than 9 cm(e.g. via 2, 3 or more ablations as described herein).

FIG. 45 is a graph illustrating a similar reduction in FPG levels, whichremain stable between one and three month post procedure.

FIG. 46 is a graph illustrating similar improvement in 2hPGmeasurements.

FIG. 47 is a graph of treatment response rates, showing that moreablations correlate to a higher percentage of positive patient outcomes.Responders, or patients with positive clinical results, are defined ashaving an HbA1c reduction of at least 0.7% at 1 month.

FIG. 48 is a graph of HbA1c percentages, measured for at least 120 dayspost treatment, showing a durable treatment effect in four out of fivepatients.

In some embodiments, the systems, devices and methods of the presentinventive concepts can be configured to maintain HbA1c below 7.5% at 150days. Note that 3 out of 4 patients are also on lower levels ofmedications than were being administered prior to the tissue treatmentprocedure.

FIG. 49 is a graph of fasting insulin change data, over 3 months,showing an improvement in the health of the beta cell.

FIG. 50 is a graph of SF-36 Mental value changes, showing improvedpatient satisfaction through better glycemic control.

In some embodiments, the systems, devices and methods of the presentinventive concepts can be configured to cause an improvement in apatient condition as measured by the clinical standard SF-36 HealthSurvey, such as an improvement in the SF-36 Mental Change score of atleast 3 points, at least 5 points or at least 10 points.

FIG. 51 is a graph of weight change in study patients, showing thatweight loss was also noticed in a dose dependent manner.

In some embodiments, the systems, devices and methods of the presentinventive concepts can be configured to achieve at least 3 kg or atleast 4 kg of weight loss.

FIG. 52 is a graph suggesting that weight loss and HbA1c are not wellcorrelated based on 30 day post treatment data.

FIG. 53 is a graph of HbA1c percentage over a twenty six week period,comparing responders R and non-responders NR.

FIG. 54 is a graph of Fasting glucose change (mg/dL) over a twenty sixweek period, comparing responders R and non-responders NR.

FIG. 55 is a graph of the change in the area under the curve of a mixedmeal tolerance test.

FIG. 56 is a graph of three patients exhibiting a large treatmenteffect, a 1.9% HbA1c improvement at 30 days.

Table D is a table presenting the large effect size of high dose cohortbeing statistically significantly better than low dose cohort.

TABLE D 1 MONTH

3 MONTHS

Human studies using the systems, devices and methods of the presentinventive concepts have demonstrated significant effectiveness, such asat least a 2% HbA1c reduction in numerous patients at 3 months, a strongindication of clinical value for patients with poorly controlled glucoselevels. The studies demonstrated excellent concordance between HbA1c andother surrogate markers such as fasting glucose and post-prandialglucose. The studies also demonstrated clinically meaningful weightloss. In some embodiments, the systems, devices and methods of thepresent inventive concepts can be used to treat naïve patients with anHbA1c of more than 6%, 6.5%, or 7%. The treatment could further includethe administration of metformin. The treatment of the present inventiveconcepts (with or without the administration of metformin or othersingle drug) could provide a therapeutic benefit to the patient betterthan a treatment comprising drug therapy alone (e.g. metformin and/oranother single drug therapy). In some embodiments, metformin and asecond-line drug can be included in the treatment of the presentinventive concepts. Treatment outcomes would include improvement inHbA1c, such as patients who achieve an improvement (i.e. reduction) ofat least 1% in HbA1c and/or patients who achieve a target HbA1c of lessthan or equal to 6.0%, 6.5%, 7.0%, or 7.5%. Treatment can also includereduction in hypoglycemic events, improved quality of life, weight loss,and combinations of the above.

Included below are results of continued studies and associated datacollected through Jul. 8, 2015.

Applicant's continued studies included the recording of various patientparameters affected by the treatment of the present inventive concepts,these parameters including but not limited to: HbA1c, fasting bloodglucose and post prandial glucose. Patients received between one andfive ablations (e.g. two to five sequential ablations performed alongtwo to five axial segments of the duodenum distal to the ampulla ofVater) on a single procedural day. The ablations were delivered by anexpandable balloon filled with hot fluid at an ablative temperature, asdescribed in detail herein. The data below in Table E were collectedfrom 39 patients with the following patient demographics:

TABLE E Characteristic Value (N = 39) Duration diabetes - yr  5.9 +/−2.2 Age - yr 53.7 +/− 7.3 Female sex - N (%) 14 (35.9) Weight - kg  85.1+/− 12.0 Height - cm 165.5 +/− 8.8  BMI - kg/m² 31.0 +/− 3.4

Procedures were completed using general anesthesia. All patients weredischarged on either the day of procedure (19/39) or after an overnightstay (20/39). The number of patients available (included) for eachfollow-up study described in FIGS. 57-61 and Table F, has the followingdistribution:

Elapsed Time since 2 14 1 3 6 9 12 Procedure Day Day Month Months MonthsMonths Months #of Pts at 39 39 39 38 34 21 21 Follow-up

The average baseline HbA1c was 9.5% (SD 1.3%) in 39 patients treatedbetween August 2013 and December 2014. HbA1c was 8.1% (SD 1.3%) 1 monthpost-procedure, 7.3% (SD 1.2%) 3 months post-procedure, and 8.1% (SD1.6%) 6 months post-procedure. These HbA1c improvements in the entirecohort are seen despite substantial masking of treatment effect due tomedication reductions in highly responsive patients in the monthsimmediately after the procedure. The average HbA1c improvement in 21patients at a 1 year follow-up is 0.5% (despite the fact that 9 out ofthese 21 patients were on reduced glycemic medicines compared to beforetheir procedure).

FIG. 57 represents the average HbA1c (%) in all available (at the timeof follow-up) subjects treated by the systems, devices and methods ofthe present inventive concepts.

The magnitude of the treatment effect was analyzed as a function oftreated dose (i.e. a dosimetric analysis was performed). Patients whohad approximately 9 cm (e.g. 9.3 cm) of duodenal tissue treated (e.g. inat least three applications of thermal energy to duodenal tissue) werelabeled to have received a “Long Segment DMR” (“LS-DMR”). Patients whohad approximately 3 cm (e.g. 3.4 cm) of duodenal tissue treated (e.g. intwo or less applications of thermal energy to duodenal tissue) werelabeled as “Short Segment DMR” (“SS-DMR”). At 1 month follow up, HbA1cwas reduced by an average of 1.7% (SD 1.0%) in LS-DMR and by 0.7% (SD1.2%) in the SS-DMR (n=28 vs 11 at 1 months). At 3 months follow up,HbA1c was reduced by an average of 2.5% (SD 1.3%) in LS-DMR and by 1.2%(SD 1.8%) in SS-DMR (n=28 vs 10 at 3 months, p<0.05 for LS vs SS).

FIG. 58 represents the average change in HbA1c (%) from baseline inpatients with LS-DMR and SS-DMR (p<0.05 for the difference at 3 months).

These clinical studies did not specify a medication treatment algorithmfor the treating diabetologist to prescribe. Note that the treatingdiabetologist was not made aware of the patients' treatment allocationwhen determining the appropriate post-procedure management strategy. Assuch, clinical decisions with respect to medication adjustments inindividual patients were made but these adjustments were not wellcontrolled with respect to a rigorous efficacy evaluation. By the timeof the six month post-procedure follow up visit, several patientsexperienced changes to their glycemic medications that would be expectedto confound efficacy analysis at later time points (see Table F below).In particular, 13 out of 26 LS-DMR patients experienced reductions inmedications and 1 patient experienced an increase in medicationprescription, compared to 4 with reductions and 3 with increases amongthe SS-DMR patients.

TABLE F Patients with Patients with Patients with Treatment reduction inno med increases in Received glycemic meds changes glycemic meds LS-DMR13 12 1 SS-DMR 4 3 3

Table F represents the number of patients in each treatment arm withmedication changes preceding the six month post-procedure follow-upvisit.

At 6 months, LS-DMR patients experienced a decline in HbA1c of 1.6% (SD1.6%) on average (n=26) despite the fact that 13 of 26 patients hadreductions in glycemic medicines that would be expected to mask themagnitude of the procedure's treatment effect. The impact of medicationreductions is evident in the analysis of fasting plasma glucose (FPG) inLS-DMR patients whose baseline HbA1c was between 7.5% and 10%. Patientswhose meds were unchanged after the procedure (“stable meds” group inleft graph below) retain stable FPG between week 12 and week 24.Patients, whose medicines were reduced, however, experienced a decay intreatment effect, the timing of which is coincident with the timing ofprescribed medication reductions.

FIG. 59 represents the average fasting plasma glucose in LS-DMR patientswith baseline HbA1c between 7.5% and 10%. The graph on the left showsFPG in all patients (“all patients”), the subset who experiencedmedication reductions (“meds decreased”) and those whose medicationswere held constant through 24 week follow up (“stable meds”). The graphon the right shows the effect of medication reductions within the first12 weeks (“meds decreased early”) compared to those with medicationreductions between week 12 and week 24 (“meds decreased late”). Thetiming of medication reductions corresponds to the timing of worseningFPG measurements.

Analysis of patients on consistent medications with a baseline HbA1c ofbetween 7.5% and 10% revealed a mean HbA1c of 8.6 (SD 0.9; n=7) atbaseline, 6.6 (SD 0.8; n=7) at 3 months, 7.2 (SD 0.6; n=6) at 6 months,and 7.3 (SD 0.3; n=4) at 12 months post procedure. These patients alsoexperienced a reduction of fasting plasma glucose of 32 mg/dl (SD 21) at3 months, 36 mg/dl (SD 24) at 6 months, and 20 mg/dl (SD 15) at 12months.

FIG. 60 represents mean HbA1c in LS-DMR patients with baseline HbA1cbetween 7.5% and 10% and consistent antidiabetic medications. Takentogether, HbA1c measurements and fasting plasma glucose levels in LS-DMRpatients with a baseline HbA1c level between 7.5% and 10% suggestdurability of treatment response through 12 months of follow up.

Patient quality of life was assessed using the SF-36 standardizedquestionnaire. At screening, LS-DMR patients had a physical compositescore (PCS) of 47 (SD 9) and a mental composite score of 46 (SD 11). At6 months, patients in the LS-DMR group saw an increase in PCS of 3.1points (SD 10; n=22) and MCS of 3.4 points (SD 14; n=22; p<0.05). Thedata suggest an improvement in the mental quality of life for poorlycontrolled diabetic patients who received LS-DMR.

Patients received a follow-up endoscopy at 1 month and/or 3 monthspost-procedure per protocol. Of the 19 patients who have received afollow-up endoscopy at 1 month, 4 patients had a reduction in heightand/or width of plicae in the duodenum near the treatment area butotherwise the mucosa appeared to be healing normally with no scarring.No luminal narrowing indicative of stenosis was present in any of the 1month endoscopies. Of the 37 patients who have received a follow-upendoscopy at 3 months, two patients had an endoscopically apparentreduction in height and/or width of plicae in the duodenum near thetreatment area. All other patients had normal endoscopies with themucosa fully healed and no evidence of scarring. No luminal narrowingwas observed in any of the 3 month endoscopies. These results indicatethat the treatment can effectively ablate the mucosa without damage tothe duodenal structure and that the mucosa regrows quickly within theablated region. The reduction in height and width of the plicae may beindicative of a reduction in the mucosal redundancy as part of thenormal healing process.

A second procedure of the present inventive concepts was performed in 3previously treated patients. There were no particular proceduralchallenges or significant adverse events associated with the secondprocedure in these three patients. Two patients had been non-respondersto initial procedure, and their second procedure did not successfullyimprove glycemic control. A third patient had an improvement in glycemiccontrol through 3 months after the first procedure, but this benefit wasnot fully sustained through the 6 month follow up visit. A repeatprocedure was performed in month 8, and the patient has since beenfollowed for six months after the second procedure. 14 months after thefirst procedure, therefore, the patient has an HbA1c of 7.3% (reductionof at least 2%) and a FPG of 100 mg/dl.

FIG. 61 represents HbA1c over time in a single patient receiving twotreatments (at month 0 and month 8, respectively).

The above summary provides clinical data on 39 patients enrolled andtreated in an initial study focused on procedural and patient safety andclinical effectiveness. The results demonstrate that the procedure canbe safely completed with devices performing as intended, that theprocedure can be well tolerated by patients, and that there exists astrong suggestion of significant clinical effectiveness. The limitednumber and transient nature of adverse events suggest that the safetyprofile of the technology and procedure is favorable. Although therewere three adverse events of duodenal stenosis formation, all wereendoscopically treated with non-emergent endoscopic balloon dilationusing techniques familiar to operators and resolved with no long-termsequelae. Other significant potential risks, including pancreatitis,perforation, bleeding, infection, or ulcer, have not been observed. Noevidence for malabsorption, severe hypoglycemia, or late complicationswas found. The experience thus far indicates a safe procedure that canbe well tolerated by patients. Mean HbA1c is reduced in treated patientsdespite net medication reductions in the patient cohort. In addition, astatistically significant dosimetric treatment response is alsoobserved, with LS-DMR patients responding more effectively than SS-DMRpatients. In addition, LS-DMR patients experienced more medicationreductions (to prophylactically avoid hypoglycemia) than SS-DMRpatients. This observation was made despite the fact that neitherpatients nor the treating endocrinologist was aware of the length oftreated tissue in individual patients. Furthermore, 23/27 LS-DMRpatients experienced an HbA1c reduction of at least 1% at 3 months offollow up, compared to 6/10 SS-DMR patients. Patients on consistentmedications with a baseline HbA1c of between 7.5% and 10% showedevidence of a durable response to treatment, with persistent reductionsin HbA1c and fasting glucose through 12 months of treatment follow up.This durable treatment response is observed even without aggressivediabetes management on the part of the treating physician, such as maybe achieved through education, lifestyle recommendations, or aggressivepharmacotherapy. The treatment of the present inventive concepts mayoffer an even more significant and durable clinical effect when coupledwith intensive medical management. The treatment effect does not appearto be weight dependent. Patients did not report any food intolerance orchange in food preference that might explain this HbA1c reduction. Whilepatients lost a small amount of weight, the magnitude of weight loss islikely not enough to explain the degree of HbA1c improvement.Furthermore, there did not appear to be any correlation between themagnitude of HbA1c reduction and weight loss.

In some embodiments, the systems, device and methods of the presentinventive concepts can reduce the need for insulin therapy in a largerproportion of patients, such as to provide durable glycemic control withor without the therapies administered to the patient prior to thetreatment of the present inventive concepts, or with a decrease indosage of one or more previously administered medications.

The systems, devices and methods of the present inventive concepts canbe configured to treat patients with microvascular disease or patientswith a high risk of microvascular disease, such as to improve patienthealth and/or eliminate or otherwise reduce the need for one or moremedications (e.g. one or more insulin medications). The treatment can beconfigured to reduce diabetic retinopathy (e.g. as shown in a reductionin diabetic retinopathy score), proteinuria and/or peripheral neuropathyseverity. Additionally or alternatively, the treatment can be configuredto reduce the effects of macrovascular disease such as myocardialinfarction, stroke, peripheral vascular disease, CV death, andcombinations of one or more of these.

The systems, devices and methods of the present inventive concepts canbe configured to treat patients with a disease or disorder of the liver,such as non-alcoholic fatty liver disease (NAFLD) and/or non-alcoholicsteatohepatitis (NASH). For example, treatment element 135 of device 100and/or treatment element 135′ of device 40 can be configured to modifyone or more axial segments of the intestine (e.g. ablate a fullcircumferential or partial circumferential axial segment of duodenalmucosal and/or submucosal tissue). In some embodiments, intestinalsubmucosal tissue of an axial segment of intestine is expanded (e.g. bydevice 30 or device 40 as described hereabove), prior to ablation of atleast the mucosal layer relatively within the expanded submucosaltissue. In some embodiments, the mucosal tissue is ablated byintroducing hot fluid into balloon 136 of device 100 or balloon 46 ofdevice 40. In some embodiments, tissue treatment element 135 of device100 or tissue treatment element 135′ of device 40 comprises an elementselected from the group consisting of: an ablative fluid delivered to aballoon or other expandable fluid reservoir; a tissue treatment elementcomprising an energy delivery element mounted to an expandable assemblysuch as an electrode or other energy delivery element configured todeliver radiofrequency (RF) energy and/or microwave energy; a lightdelivery element configured to deliver laser or other light energy; afluid delivery element (e.g. a sponge or a nozzle) configured to deliverablative fluid directly onto tissue; a sound delivery element such as aultrasonic and/or subsonic sound delivery element; and combinationsthereof, as described in detail herein. In some embodiments, a patientwith NAFLD and/or NASH is selected and treated as described herebelow inreference to FIG. 7.

Applicant's clinical studies described hereabove have demonstratedpotential benefit to patients with a liver disease or disorder such asNAFLD and/or NASH. FIG. 62 exhibits an improvement (reduction) in thelevel of liver transaminases found in the treated patients.

FIG. 62 represents an improvement (reduction) in the level (expressed inmg/dL) of two liver transaminases, aspartate transaminase (AST) andalanine transaminase (ALT), that resulted after a mucosal treatment ofthe present inventive concepts. The data presented in FIG. 62 represents13 patients through week 24, and 8 (of the 13) patients through week 48.The data presented is representative of patients that had at least 3 cmof duodenal mucosa treated, such as when two or more axial segments ofduodenal mucosa were treated to achieve a cumulative treated length ofat least 6 cm or at least 9 cm. Pre-procedure, each patient had elevatedbaseline levels of AST and ALT as shown, which is indicative ofinflammation of the liver. The AST and ALT levels were sustainablyreduced after treatment of multiple segments of duodenal mucosa usingthe systems, devices and methods of the present inventive concepts.These reductions correlate to one or more of: improvement in steatosis,reduced inflammation of the liver and/or reduced fibrosis of the liver.In some embodiments, the methods of the present inventive concepts areconfigured to improve steatosis, reduce cirrhosis, reduce inflammationof the liver, reduce fibrosis of the liver and/or reduce liver failure.

FIGS. 3-33 described herebelow illustrate various configurations for thesystems and catheters of the present inventive concepts, such as system10 and catheter 100 described hereabove in reference to FIG. 1, andsystem 10 and catheters 100, 20, 30 and/or 40 described hereabove inreference to FIG. 2. In the below figures, each system 10 and catheter100 can comprise one or more components of similar construction andarrangement to system 10 and catheters 100, 20, 30 and/or 40 of FIG. 1and/or FIG. 2, whether shown in the associated figure or not. In some ofthe figures, one or more conduits 111 have been removed for illustrativeclarity, such as one or more fluid, translatable rod, signal and/orpower transporting conduits attached to one or more functional elements,inflatable balloons or other expandable elements and/or other componentsof the system 10 and/or catheter 100 illustrated in the associatedfigure. Each of the functional assemblies 130 can be constructed andarranged to perform a first step of a medical procedure (e.g. a tissueablation procedure, a tissue expansion procedure and/or a tissuediagnostic procedure) at a first axial segment of the intestine, andsubsequently perform at least a second step of the medical procedure ata second axial segment of the intestine, at a location proximal ordistal to the first axial segment of the intestine. In some embodiments,a sequence of three or more steps at three or more axial segments can beperformed. In some embodiments, both a tissue expansion and a tissueablation are performed at each selected axial segment of the intestine.

Each functional assembly 130 can comprise a balloon 136 or otherexpandable element, such as: a radially expandable cage or stent; one ormore radially deployable arms; an expandable helix; an unfurlablecompacted coiled structure; an unfurlable sheet; and/or an unfoldablecompacted structure.

Referring now to FIG. 3, an anatomic view of a system for performing amedical procedure comprising a catheter and a sheath for inserting thecatheter into the intestine of the patient is illustrated, consistentwith the present inventive concepts. System 10 comprises catheter 100and sheath 90 (e.g. an introducer sheath), each of which has beeninserted through the mouth of the patient and advanced through thestomach to a location distal to the patient's pylorus. System 10 canfurther comprise guidewire 60. System 10 can comprise one or more othercomponents, such as console 200 and other components not shown, butsimilar to those described hereabove in reference to system 10 of FIG. 1or system 10 of FIG. 2. Catheter 100 comprises port 103, handle 102,shaft 110, bulbous tip 115 and other components, such as those describedhereabove in reference to catheter 100 of FIG. 1, or catheters 100, 20,30 and/or 40 of FIG. 2.

Sheath 90 comprises an elongate, flexible tube, shaft 99, and an inputport 91 on the proximal end of shaft 99. Input port 91 can include afunnel-shaped or other opening configured to assist in the introductionof catheter 100 or other devices into a lumen of sheath 90. Input port91, or another proximal portion of sheath 90, can be configured toattach sheath 90 to an endoscope or other body introduction device (e.g.device 50 described herein). In some embodiments, input port 91comprises a strain relief configured to attach sheath 90 to a bodyintroduction device. Bite block 98 can be positioned about shaft 99 at alocation relatively proximate to input port 91. Positioned along adistal portion of shaft 99 are one or more anchor elements, such asanchor elements 95 a and 95 b shown. Anchor elements 95 a and 95 b cancomprise a radially expandable structure, such as an expandablestructure selected from the group consisting of: an inflatable balloon;a radially expandable cage or stent; one or more radially deployablearms; an expandable helix; an unfurlable compacted coiled structure; anunfurlable sheet; an unfoldable compacted structure; and combinations ofone or more of these. Anchor elements 95 a and 95 b have been positionedat locations proximal and distal, respectively, to the pylorus, andsubsequently radially expanded, such as to anchor distal end 92 of shaft99 at a location distal to the ampulla of Vater (e.g. to avoidinadvertently treating or otherwise adversely affecting the ampulla ofVater and/or tissue proximate the ampulla of Vater). In someembodiments, anchor element 95 a and/or 95 b can be configured to beinflated within the duodenal bulb of the patient.

In some embodiments, shaft 99 comprises a variable stiffness along itslength, such as a more flexible distal portion constructed and arrangedto be positioned distal to the pylorus, than a portion that would bepositioned proximal to the pylorus (e.g. to avoid a “slack” segment inthe stomach when advancing catheter 100 through shaft 99). In someembodiments, shaft 99 comprises a variable stiffness as describedherebelow in reference to shafts 110′ and 110″ of FIGS. 27 and 28,respectively. In some embodiments, shaft 99 comprises a shaft includinga braided portion. In some embodiments, sheath 90 comprises anon-circular cross-section (e.g. as described herebelow in reference toFIG. 32 or 33), such as to efficiently couple with an endoscope or otherbody introduction device (e.g. device 50 described herein), such as anon-circular cross-section selected from the group consisting of: oval;kidney shape; and combinations thereof.

FIGS. 3A and 3B illustrate side sectional and end sectional views,respectively, of the distal portion of sheath 90, without an insertedcatheter 100 nor an inserted guidewire 60. Shaft 99 includes a lumen 94,such as a lumen constructed and arranged to slidingly receive aguidewire, such as guidewire 60, to permit over-the-wire advancement andretraction of sheath 90. Shaft 99 further includes working channel 93,such as a lumen constructed and arranged to slidingly receive atreatment or diagnostic device, such as catheter 100 as describedherein. In some embodiments, working channel 93 comprises a diametergreater than or equal to 10 mm, or 20 mm. In some embodiments, sheath 90is advanced to a desired location (e.g. with or without catheter 100residing within working channel 93), and subsequently bulbous tip 115 ofcatheter 100 is advanced out of distal end 92 of sheath 90. Shaft 99 canfurther comprise a lumen 96, which can be configured as an inflationlumen when one or more of anchor elements 95 a or 95 b comprise aballoon or other inflatable structure. Alternatively, lumen 96 can beconstructed and arranged to receive a translatable rod or otherfilament, such as when anchor element 95 a and/or 95 b comprise anexpandable scaffold, radially deployable arm or other structure whoseexpansion and contraction is controlled by the translation of thefilament. Working channel 93 and/or lumen 94 can be configured as a portfor delivering and/or extracting fluids from the intestine (e.g. toinsufflate and/or desufflate, respectively, a segment of the intestine).

In some embodiments, system 10 of FIG. 3 comprises one or more sensors,such as one or more functional elements 109, 119, 139, 209, 229 and/or309 described hereabove in reference to FIG. 1, that have beenconfigured as a sensor. These one or more sensors can be configured toprovide a signal, such as a signal used to adjust one or more console200 settings (e.g. console settings 201) of the present inventiveconcepts. In some embodiments, functional assembly 130 comprises one ormore functional elements, such as functional element 139 a, 139 b and/or139 c described hereabove in reference to FIG. 1, such as a functionalelement constructed and arranged to perform a therapeutic and/ordiagnostic medical procedure, as described herein.

Referring now to FIGS. 4A, 4B and 4C, anatomical, side sectional viewsof a series of steps for performing a medical procedure are illustrated,consistent with the present inventive concepts. System 10 comprisescatheter 100, a body introducer such as endoscope 50 a, and a tool forextracting fluid, fluid transport tool 71. System 10, catheter 100 andendoscope 50 a can be of similar construction and arrangement to thesimilar components described hereabove in reference to FIG. 1 or FIG. 2.Endoscope 50 a comprises one or more working channels, such as lumens 51and 54 shown. The distal portion of catheter 100 (including the distalportion of shaft 110) has been inserted through and out of lumen 51, andfunctional assembly 130 has been radially expanded, such as to perform adiagnostic or therapeutic procedure on an axial segment of intestinaltissue in contact with functional assembly 130. Functional assembly 130can be configured to perform one or more medical procedures as describedherein (e.g. a therapeutic procedure such as a tissue ablation procedureand/or a tissue expansion procedure, and/or a diagnostic procedure).Functional assembly 130 can comprise an extending shaft, such as anextending shaft with a bulbous tip such as bulbous tip 115 describedhereabove in reference to FIG. 1 or FIG. 2.

Tool 71 has been advanced through lumen 54 of endoscope 50 a and can bepositioned proximate functional assembly 130 as shown in FIG. 4A, distalto functional assembly 130 as shown in FIG. 4B, and positioned alongsidefunctional assembly 130 (i.e. between the proximal and distal ends offunctional assembly 130) as shown in FIG. 4C. Tool 71 can be activated(e.g. via a control on a proximal end of tool 71 or via a control of anattached console such as console 200 described hereabove), such as toextract fluids (e.g. liquids or gases) from within an intestinal segmentproximate functional assembly 130, such as to cause the wall of theintestine to make contact and/or increase contact with functionalassembly 130. Alternatively or additionally, extraction of fluids (e.g.desufflation) can be performed with one or more lumens of endoscope 50 aand/or one or more lumens or ports of catheter 100 (e.g. as describedherebelow in reference to FIGS. 5A and 5B).

In some embodiments, tool 71 is alternatively or additionallyconstructed and arranged to deliver fluids (e.g. a gas) into anintestinal segment proximate (e.g. proximal to and/or distal to)functional assembly 130, such as to insufflate the intestine, such as todecrease contact between functional assembly 130 and the intestinalwall.

In some embodiments, tool 71 is alternatively or additionallyconstructed and arranged to produce a patient image, such as when tool71 comprises a camera device (e.g. a visible light camera or infraredcamera). In some embodiments, tool 71 alternatively or additionallycomprises a tool selected from the group consisting of: a fluidinjection device such a tool comprising a needle; a heating tool; acooling tool (e.g. a tool comprising a Peltier element); a light; avibrational tool, an agitating tool; and combinations of one or more ofthese.

In some embodiments, system 10 of FIGS. 4A-C comprises one or moresensors, such as one or more functional elements 109, 119, 139, 209, 229and/or 309 described hereabove in reference to FIG. 1, that have beenconfigured as a sensor. These one or more sensors can be configured toprovide a signal, such as a signal used to adjust one or more console200 settings (e.g. console settings 201) of the present inventiveconcepts. In some embodiments, functional assembly 130 comprises one ormore functional elements, such as functional element 139 a, 139 b and/or139 c described hereabove in reference to FIG. 1, such as a functionalelement constructed and arranged to perform a therapeutic and/ordiagnostic medical procedure, as described herein.

Referring now to FIGS. 5A and 5B, end and side views of the distalportion of a catheter including recessed ports, shaft-located vacuumports, and an inflatable distal tip are illustrated, consistent with thepresent inventive concepts. Catheter 100 comprises shaft 110, functionalassembly 130 (shown in its expanded state), and other components, suchas one or more components of similar construction and arrangement tothose described hereabove in reference to catheter 100 of FIG. 1 or FIG.2, such as one or more conduits 111, some of which have been removed forillustrative clarity (three conduits 111 shown in FIG. 5B). In someembodiments, bulbous tip 115 is positioned on the distal end of catheter100 as shown. Functional assembly 130 is configured to radially expandand contract, and can comprise an expandable element selected from thegroup consisting of: an inflatable balloon such as balloon 136 shown; aradially expandable cage or stent; one or more radially deployable arms;an expandable helix; an unfurlable compacted coiled structure; anunfurlable sheet; an unfoldable compacted structure; and combinations ofone or more of these as described herein. Functional assembly 130 isshown in a radially expanded state in FIGS. 5A and 5B.

In some embodiments, functional assembly 130 includes one or morerecesses, such as the three recesses 133 (e.g. a recess of balloon 136)shown in FIG. 5A. Positioned within each recess 133 is a port 137,configured to capture or at least engage tissue when a vacuum is appliedto each port 137, such as via one or more conduits such as conduits 111described hereabove. Recesses 133 can be sized such that port 137 isrelatively flush with the surface of an expanded functional assembly 130or is otherwise constructed and arranged to limit the radial extensionof each port 137 from the outer surface of an expanded functionalassembly 130, such as to allow the surface of functional assembly 130proximate each port 137 to sufficiently contact intestinal wall tissue(e.g. to avoid “tenting” of the tissue around each port 137), and/or toavoid trauma to intestinal wall tissue proximate each port 137.

In some embodiments, catheter 100 comprises one or more ports configuredto deliver and/or extract fluids, such as to perform an insufflation ordesufflation step, such as to change the level of contact betweenfunctional assembly 130 and the intestinal wall (e.g. desufflation toachieve sufficient apposition between functional assembly 130 and theintestinal wall to ablate target tissue), as described herein. Catheter100 of FIG. 5B comprises port 112 a positioned on shaft 110 proximal tofunctional assembly 130 and port 112 b positioned distal to functionalassembly 130. Ports 112 a and 112 b are fluidly connected to conduits111 a and 111 b, respectively, such that fluid can be extracted (e.g.liquids or gases extracted by console 200 described hereabove) fromwithin the intestine by ports 112 a and/or 112 b, such as to desufflatethe intestine proximal and/or distal to functional assembly 130.Alternatively or additionally, fluid can be delivered to the intestineby ports 112 a and/or 112 b, such as to insufflate and/or desufflate theassociated segment of the intestine. Catheter 100 can comprise one ormore ports positioned along functional assembly 130, such as ports 137which include openings 138 shown in FIG. 5B. Fluid can be delivered orextracted, such as to insufflate or desufflate, respectively, asdescribed hereabove in reference to ports 112 a and 112 b. Alternativelyor additionally, ports 137 including openings 138 can be configured tocapture or at least frictionally engage tissue (e.g. wall tissue of theintestine), such as to complete a tissue expansion procedure and/or toanchor the distal portion of catheter 100, each as described herein. Insome embodiments, functional assembly 130 of FIGS. 5A-B is configured toboth expand one or more tissue portions and ablate one or more tissueportions. In some embodiments, ports 112 a, 112 b or another componentof catheter 100 or system 10 (e.g. a working channel of introductiondevice 50) is configured to automatically insufflate and/or desufflate,such as an insufflation and/or desufflation triggered by a recording bya sensor of system 10 (e.g. a sensor as described herein, and whosesignal is processed by algorithm 251 to automatically initiate thedelivery and/or extraction of fluids from the intestine).

In some embodiments, catheter 100 comprises a bulbous distal tip, suchas a tip configured to be inflated or otherwise expanded, such asinflatable tip 115′ shown in FIG. 5A-B which can comprise a balloon orother expandable structure. Inflatable tip 115′ can be fluidly attachedto conduit 111 c which can travel proximally to be attached to aninflation source, such as a pumping assembly 225 and reservoir 220 ofconsole 200 described hereabove in reference to FIG. 1. Inflatable tip115′ can be configured to expand to a diameter of at least 4 mm and/or adiameter of no more than 15 mm, such as an inflation that occurs afterinflatable tip 115′ exits a lumen (e.g. a lumen of an introductiondevice such as endoscope 50 a or sheath 90 described hereabove inreference to FIG. 1).

In some embodiments, catheter 100 comprises functional element 119positioned in, on and/or within shaft 110. Functional element 119 cancomprise a heating or cooling element configured to modify and/orcontrol the temperature of fluid entering balloon 136.

In some embodiments, catheter 100 of FIGS. 5A-B comprises one or moresensors, such as one or more functional elements 109, 119 and/or 139described hereabove in reference to FIG. 1, that have been configured asa sensor. These one or more sensors can be configured to provide asignal, such as a signal used to adjust one or more console 200 settings(e.g. console settings 201) of the present inventive concepts. In someembodiments, functional assembly 130 comprises one or more functionalelements, such as functional element 139 a, 139 b and/or 139 c describedhereabove in reference to FIG. 1, such as a functional elementconstructed and arranged to perform a therapeutic and/or diagnosticmedical procedure, as described herein.

Referring now to FIGS. 6A and 6B, anatomical, side sectional views ofthe distal end of a catheter comprising a functional assembly configuredto expand to multiple geometric configurations are illustrated,consistent with the present inventive concepts. Catheter 100 comprisesshaft 110, functional assembly 130, and other components, such as one ormore components of similar construction and arrangement to thosedescribed hereabove in reference to catheter 100 of FIG. 1 or FIG. 2,such as one or more conduits 111 which have been removed forillustrative clarity. Functional assembly 130 can comprise balloon 136and can be configured to radially expand and contract, such as radialexpansion that is limited or is otherwise reduced at a mid-portion (e.g.tissue contacting portion) of balloon 136. Balloon 136 comprisesproximal wall 131 and distal wall 132. In FIG. 6A, functional assembly130 has been expanded (i.e. balloon 136 has been inflated with a firstvolume of fluid) to a first level of expansion, and proximal wall 131and distal wall 132 each relatively remain within a single plane.Balloon 136 can be constructed and arranged such that proximal wall 131and/or distal wall 132 deflect (as shown in FIG. 6B) when additionalfluid is delivered into balloon 136, such as to prevent furtherexpansion of portions of balloon 136 in contact with the intestinal wall(e.g. to prevent additional force on the intestinal wall and/or unevenapposition of balloon 136 with the intestinal wall).

In some embodiments, balloon 136 further comprises a radial expansionlimiting element, such as restrictor 134, which can comprise a tubularrestrictor (e.g. circumferential mesh) positioned on an inner surfaceof, outer surface of and/or within the wall of balloon 136.

In some embodiments, catheter 100 of FIGS. 6A-B and/or one or morecomponents attached to catheter 100 comprises one or more sensors, suchas one or more functional elements 109, 119, 139, 209, 229 and/or 309described hereabove in reference to FIG. 1, that have been configured asa sensor. These one or more sensors can be configured to provide asignal, such as a signal used to adjust one or more console 200 settings(e.g. console settings 201) of the present inventive concepts. In someembodiments, functional assembly 130 comprises one or more functionalelements, such as functional element 139 a, 139 b and/or 139 c describedhereabove in reference to FIG. 1, such as a functional elementconstructed and arranged to perform a therapeutic and/or diagnosticmedical procedure, as described herein.

Referring now to FIG. 7, an anatomical, side sectional view of thedistal end of a catheter comprising a functional assembly including aballoon with varied wall thickness is illustrated, consistent with thepresent inventive concepts. Catheter 100 comprises shaft 110, functionalassembly 130 (shown in its expanded state), and other components, suchas one or more components of similar construction and arrangement tothose described hereabove in reference to catheter 100 of FIG. 1 or FIG.2, such as one or more conduits 111 which have been removed forillustrative clarity. Functional assembly 130 can comprise balloon 136and can be configured to radially expand and contract. Balloon 136comprises one or more thick wall portions 134 a, each of which cancomprise a portion of the wall of balloon 136 that is thicker than oneor more other wall portions of balloon 136. Thick wall portion 134 a cancomprise one or more thick wall portions positioned at a proximal and/ordistal location of the tissue-contacting portion of balloon 136 (e.g.one or more wall portions thicker than the wall at a mid-portion ofballoon 136). Thick wall portion 134 a can function as an insulatingportion constructed and arranged to limit transfer of energy (e.g. heatenergy or cryogenic energy) between functional assembly 130 andintestinal wall tissue at one or more locations of functional assembly130 (e.g. at the proximal and distal tissue-contacting portions ofballoon 136).

In some embodiments, catheter 100 of FIG. 7 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 8, an anatomical, side sectional view of thedistal end of a catheter comprising a functional assembly including aninsulating element is illustrated, consistent with the present inventiveconcepts. Catheter 100 comprises shaft 110, functional assembly 130(shown in its expanded state), and other components, such as one or morecomponents of similar construction and arrangement to those describedhereabove in reference to catheter 100 of FIG. 1 or FIG. 2, such as oneor more conduits 111 which have been removed for illustrative clarity.Functional assembly 130 can comprise balloon 136 and can be configuredto radially expand and contract. Functional assembly 130 comprises oneor more insulating elements 134 b, positioned on the inner surface,outer surface and/or within the wall of balloon 136. Insulating elements134 b can be positioned at a proximal and/or distal location of thetissue-contacting portion of balloon 136. Insulating element 134 b canbe constructed and arranged to limit transfer of energy (e.g. heatenergy or cryogenic energy) between functional assembly 130 andintestinal wall tissue at one or more locations of functional assembly130 (e.g. at the proximal and distal tissue-contacting portions ofballoon 136).

In some embodiments, catheter 100 of FIG. 8 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 9, a side view of a catheter comprising a tissuedissecting assembly is illustrated, consistent with the presentinventive concepts. Catheter 100 comprises shaft 110, functionalassembly 130 (shown in its expanded state), and other components, suchas one or more components of similar construction and arrangement tothose described hereabove in reference to catheter 100 of FIG. 1 or FIG.2, such as one or more conduits 111 which have been removed forillustrative clarity. Shaft 110 comprises shaft 110 a, 110 b and 110 d.Shaft 110 can comprise additional shafts, such as a shaft 110 c notshown but constructed and arranged such that shafts 110 a, 110 b and 110c are separated by approximately 120°. Catheter 100 can comprise bulboustip 115 as shown. Functional assembly 130 can comprise an inflatableballoon, balloon 136. Catheter 100 comprises one or more tools 141 (twoshown in FIG. 9), each of which is slidingly received by a shaft (e.g.shafts 110 a and 110 b shown). Each tool 141 can be operably connectedto a translatable shaft or other translatable conduit, such as a conduit111 comprising a translatable shaft as described hereabove in referenceto FIG. 1.

FIG. 9A illustrates a magnified view of one of the tools 141 of catheter100 of FIG. 9. The distal portions of shafts 110 a and 110 b areattached along functional assembly 130 (e.g. attached along balloon 136)and the distal end of each shaft 110 a and 110 b is positioned near thedistal end of functional assembly 130.

In some embodiments, tools 141 comprise a sharp instrument (e.g. blade,needle or other cutting element) configured to dissect tissue, such as adissection that occurs when functional assembly 130 is advanced within alumen of the intestine while tools 141 are engaged (e.g. extendeddistally). In some embodiments, tool 141 comprises a tissue dissectionelement selected from the group consisting of: blunt dissector; needle;needle knife; fluid delivery element; and combinations of one or more ofthese. In some embodiments, tool 141 comprises a vacuum port, such asport 137 described herein. In some embodiments, tools 141 arealternatively or additionally configured to deliver an agent to tissueand/or to deliver energy to tissue, such as an agent selected from thegroup consisting of: EtOH; hypertonic saline; Sotradecol; andcombinations of one or more of these. Tools 141 can be configured toremove and/or treat a full or partial circumferential axial segment ofintestinal tissue, such as to remove the mucosal tissue along one ormore axial segments of intestine (e.g. duodenum) to provide atherapeutic benefit (e.g. to treat a disease or disorder such asdiabetes).

In some embodiments, catheter 100 of FIG. 9 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIGS. 10A-D, side views of a distal portion of a system10 including a sheath with a sealing distal end are illustrated,consistent with the present inventive concepts. System 10 comprisessheath 90 and catheter 100. System 10 can comprise one or more othercomponents, such as console 200 and other components not shown, butsimilar to those described hereabove in reference to system 10 of FIG. 1or FIG. 2. Catheter 100 comprises shaft 110, functional assembly 130(shown in its compacted state in FIGS. 10A-C, and in its expanded statein FIG. 10D), and other components, such as one or more components ofsimilar construction and arrangement to those described hereabove inreference to catheter 100 of FIG. 1 or FIG. 2, such as one or moreconduits 111 which have been removed for illustrative clarity. Catheter100 can comprise bulbous tip 115 positioned on the distal end of shaft110. Sheath 90 comprises distal end 92 and sealing element 97 positionedon or about distal end 92. Sealing element 97 comprises one or moreelastic or otherwise resilient materials constructed and arranged totend to close upon itself, such as to seal (e.g. partially seal and/orreduce tissue or fluid ingress into sheath 90) one or more openings onthe distal end of sheath 90. Sealing element 97 can be furtherconstructed and arranged to stretch or otherwise open, such as to allowa device to pass therethrough, such as the distal portion of catheter100, and form a seal (e.g. form a partial seal and/or reduce tissue orfluid ingress between sheath 90 and an inserted device) around theportion of the device passing through sealing element 97.

In FIG. 10A, bulbous tip 115 of catheter 100 remains within a lumen ofsheath 90, and sealing element 97 is in a resiliently biased position(e.g. closed or partially closed). In FIG. 10B, catheter 100 has beenadvanced such that bulbous tip 115 extends partially through sealingelement 97, which has resiliently expanded to accommodate bulbous tip115. In FIG. 10C, catheter 100 has been further advanced such thatbulbous tip 115 has fully passed through sealing element 97, and sealingelement 97 has partially collapsed to surround shaft 110 (e.g. to form aseal or partial seal and/or to limit tissue or fluid ingress betweenshaft 110 and sealing element 97). In FIG. 10D, catheter 100 has beenfurther advanced such that functional assembly 130 has passed throughsealing element 97, and functional assembly 130 has been radiallyexpanded.

Sealing element 97 can be constructed and arranged to provide a seal ornear-seal (generally “seal”) around one or more device componentspositioned within sealing element 97, such as to prevent capture oftissue between sealing element 97 and the inserted component, and/or tolimit fluids passing therebetween. Sealing element 97 can comprise oneor more materials, such as metals (e.g. superelastic metals, metal coilsor metal cages), plastic, elastomers, and the like. In some embodiments,sealing element 97 is connected to one or more controls on the proximalend of sheath 90, such as to control the orifice or other shape ofsealing element 97, such as when sealing element 97 comprises amechanically-actuated valve actuated by a control rod, or when sealingelement 97 comprises an electrically-actuated valve connected to anelectrical wire (e.g. a solenoid valve or a valve comprising heatactivated shape memory metal such as heat-activated nickel titaniumalloy).

In some embodiments, system 10 of FIGS. 10A-D comprises one or moresensors, such as one or more functional elements 109, 119, 139, 209, 229and/or 309 described hereabove in reference to FIG. 1, that have beenconfigured as a sensor. These one or more sensors can be configured toprovide a signal, such as a signal used to adjust one or more console200 settings (e.g. console settings 201) of the present inventiveconcepts. In some embodiments, functional assembly 130 comprises one ormore functional elements, such as functional element 139 a, 139 b and/or139 c described hereabove in reference to FIG. 1, such as a functionalelement constructed and arranged to perform a therapeutic and/ordiagnostic medical procedure, as described herein.

Referring now to FIG. 11, a side view of the distal portion of acatheter including multiple shafts arranged in a spiraled configurationis illustrated, consistent with the present inventive concepts. Catheter100 comprises shaft 110, functional assembly 130 (shown in its expandedstate), and other components, such as one or more components of similarconstruction and arrangement to those described hereabove in referenceto catheter 100 of FIG. 1 or FIG. 2, such as one or more conduits 111,some of which have been removed for illustrative clarity (three conduits111 shown in FIG. 11). Functional assembly 130 can comprise aninflatable balloon, balloon 136. Shaft 110 of FIG. 11 comprises multipleshafts, such as shafts 110 a, 110 b, 110 c, and 110 d shown. Shafts 110a-c are each arranged in a helical, spiral and/or otherwisetwisted-shaft geometry (hereinafter spiraled, helix or helicalconfiguration) about shaft 110 d. Shaft 110 d comprises one or morelumens or tubes, such as a lumen constructed and arranged to inflate orotherwise expand functional assembly 130. Ports 137 a, 137 b, and 137 c(singly or collectively port 137) are attached to functional assembly130, such as with equal 120° spacing along a circumference of balloon136 and positioned at a relative mid-portion of balloon 136. Shafts 110a-c are operably attached to ports 137 a-c, respectively. Shafts 110 a-ccan each comprise one or more lumens or tubes, such as a vacuum lumenconfigured to deliver a vacuum to an attached port 137 and a lumenconfigured to slidingly receive a conduit 111 which includes a fluiddelivery element 139 c (for example a needle, not shown) at its distalend, such as is described hereabove in reference to FIG. 1 or FIG. 2.

As described above, in the embodiment of FIG. 6, shafts 110 a-c arearranged in a helical arrangement along at least a portion of the lengthof shaft 110. In this helical arrangement, relatively similaradvancement of the proximal ends of multiple conduits 111 causesrelatively similar advancement of the distal ends of multiple conduits111 (i.e. relatively similar advancement of multiple fluid deliveryelements 139 c), even when shaft 110 is in a curvilinear geometry. Thisequilibration is due to the helix causing each shaft 110 a-c totransition between the inner and outer radii of one or more curves whencatheter 100 has been inserted through tortuous or otherwise curvilinearanatomy. If the shafts 110 a-c were arranged in a relatively co-linear,non-helical arrangement, a lumen on the inside of a curve would traversea shorter path length than a lumen on the outside of the curve. Thehelical arrangement of shafts 110 a-c ensures that no tube or lumen (orfilament within the tube or lumen) is consistently on either the insideor outside of a curved portion of shaft 110.

Shafts 110 a-c can be arranged in a helix with a uniform or non-uniformpitch. In some embodiments, shafts 110 a-c are arranged with a pitchsuch that each shaft spirals (e.g. rotates or helically traverses)between 360° (1 turn) and 1440° (4 turns) about a central axis (e.g.shaft 110 d) along at least a portion of the length of shaft 110. Insome embodiments, one or more continuous segments of shaft 110 comprisea helical portion. In some embodiments, shaft 110 comprises anarrangement of shafts 110 a-c which spiral approximately 540° (1.5turns) about shaft 110 d along at least a portion of the length of shaft110. In some embodiments, the helical portion of shaft 110 is a segmentproximate functional assembly 130 (e.g. in a distal portion of shaft110). This helical arrangement of shafts 110 a-c ensures that if shaft110 is coiled in one or more directions, none of the lumens of shafts110 a-c are always on the inside or outside of a curved portion of shaft110, minimizing differences in the lumen path lengths caused byshortening of a lumen in compression (inside of a curve) and/orextending of a lumen in tension (outside of a curve). Similar lumen pathlengths result in similar travel distances in one or more filamentswithin shafts 110 a-c, such as similar travel distances of conduits 111during advancement and/or retraction of the associated fluid deliveryelement 139 c into and/or out of ports 137. The one or more helicalportions of shaft 110 described hereabove enable the translationprovided by a control on a proximal handle (e.g. handle 102 of FIG. 1 orFIG. 2) to accommodate shaft 110 a-c lumen path length variations thatresult when shaft 110 is in a curved geometry.

In some embodiments, catheter 100 of FIG. 11 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 12, a side view of a distal portion of a cathetercomprising ports mounted on a tapered proximal portion of a functionalassembly is illustrated, consistent with the present inventive concepts.Catheter 100 comprises shaft 110, functional assembly 130 (shown in itsexpanded state), and other components, such as one or more components ofsimilar construction and arrangement to those described hereabove inreference to catheter 100 of FIG. 1 or FIG. 2, such as one or moreconduits 111, some of which have been removed for illustrative clarity(two conduits 111 shown in FIG. 12). Catheter 100 can comprise bulboustip 115 on its distal end. Shaft 110 comprises shafts 110 a, 110 b and110 d shown. Shaft 110 can comprise additional shafts, such as a shaft110 c not shown but constructed and arranged such that shafts 110 a, 110b and 110 c are separated by approximately 120°. In some embodiments,shafts 110 a, 110 b and/or 110 d are constructed and arranged to allowan imaging device such as an endoscope as described herein to bepositioned proximate functional assembly 130, such as to be in betweenportions of one or more shafts 110 a, 110 b and/or 110 d. For example,shafts 110 a and/or 110 b can begin to diverge (e.g. when functionalassembly 130 is in an expanded or partially expanded state) away from acentral shaft 110 d and toward a tissue contacting portion of functionalassembly 130, the divergence positioned at least 3 cm, 6 cm or 9 cm fromthe proximal end of functional assembly 130, such as to create space forpositioning the distal end of an endoscope relatively proximatefunctional assembly 130. Functional assembly 130 can comprise aninflatable balloon, balloon 136, which can be connected to an inflationlumen or tube, conduit 111 a.

Functional assembly 130 of FIG. 12 comprises one or more ports 137 thatare mounted to a proximal portion of functional assembly 130, such as ona tapered proximal wall 131 of balloon 136. Positioning of ports 137 onwall 131 avoid ports 137 being on a tissue contacting surface of balloon136 (e.g. to avoid an uneven or undesired transfer of energy fromballoon 136 to tissue, such as when balloon 136 is configured to receivefluid at an ablative temperature). In some embodiments, the proximalportion of functional assembly 130 comprises a taper angle TA between80° and 10°, such as a taper angle TA between 60° and 20°. In someembodiments, the distal portion of functional assembly 130 comprises atapered portion (as shown), such as a tapered portion with a taper angleTA between 80° and 10°, such as between 60° and 20°. Each port 137comprises an opening 138, such as an opening sized to capture orotherwise engage tissue against and/or within port 137 when vacuum isapplied to port 137, such as a vacuum applied via one or more attachedvacuum delivery conduits 111 (not shown but such as those describedherein). In some embodiments, shafts 110 a and 110 b and one or moreother shafts comprise a lumen configured to slidingly receive a separatetube, (e.g. conduit 111 b within shaft 110 b) such as a translatabletube with a fluid delivery element 139 c positioned on the distal end ofthe tube. In some embodiments, each fluid delivery element 139 c is ofsimilar construction and arrangement to fluid delivery element 139 c ofFIG. 1, such as to deliver fluid into tissue engaged and/or capturedagainst and/or within port 137. Positioning of ports 137 on the proximalend (e.g. proximal taper) of functional assembly 130 can be configuredto limit the depth of a needle or other fluid delivery element 139 cinto the wall of the intestine.

In some embodiments, catheter 100 of FIG. 12 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 13, a side view of a distal portion of a cathetercomprising needle-directing ports mounted on a proximal end of afunctional assembly is illustrated, consistent with the presentinventive concepts. Catheter 100 comprises shaft 110, functionalassembly 130 (shown in its expanded state), and other components, suchas one or more components of similar construction and arrangement tothose described hereabove in reference to catheter 100 of FIG. 1 or FIG.2, such as one or more conduits 111, some of which have been removed forillustrative clarity (two conduits 111 shown in FIG. 13). Catheter 100can comprise bulbous tip 115 on its distal end. Shaft 110 comprisesmultiple shafts, such as shafts 110 a, 110 b and 110 d shown. Shaft 110can comprise additional shafts, such as a shaft 110 c not shown butconstructed and arranged such that shafts 110 a, 110 b and 110 c areseparated by approximately 120°. Functional assembly 130 can comprise aninflatable balloon, balloon 136, such as a balloon which can be inflatedby fluid delivered by an inflation tube, conduit 111 d shown. Functionalassembly 130 of FIG. 13 comprises one or more needletrajectory-directing ports 137 that are mounted to a proximal end offunctional assembly 130, such as on a tapered proximal portion ofballoon 136. In some embodiments, functional assembly 130 comprises ataper angle TA between 80° and 10°, such as a taper angle TA between 60°and 20°. Each port 137 is configured to slidingly receive a fluiddelivery element 139 c (e.g. a needle), as well as a tissue stop 142 anda translatable tube (e.g. conduit 111 b shown within shaft 110 b)fluidly attached to fluid delivery element 139 c. Conduit 111 b, tissuestop 142 and fluid delivery element 139 c are configured to translatewithin port 137 (e.g. port 137 slidingly receives fluid delivery element139 c), such as when the proximal end of fluid delivery conduit 111 b isadvanced and/or retracted (e.g. via a control on a proximal handle asdescribed herein). Fluid delivery element 139 c is shown in an advancedstate in FIG. 13, and retraction of conduit 111 b can position thedistal end of fluid delivery element 139 within port 137 or at alocation more proximal than port 137.

Each tissue stop 142 can comprise a travel limiting element (e.g. adonut-shaped or c-shaped element) that at least partiallycircumferentially surrounds fluid delivery element 139 c. Tissue stop142 can be mechanically fixed to fluid delivery element 139 c, such asvia a crimp, swage, weld or adhesive. Each tissue stop 142 comprises adiameter or other sufficient surface area configured to limit travel ofthe surrounded fluid delivery element 139 c into tissue (e.g. to preventextension beyond submucosal tissue or beyond an outer layer of theintestine). Each fluid delivery element 139 c extends a distance D_(E)beyond the attached tissue stop 142. Distance D_(E) can be chosen suchas to inject fluid a predetermined depth beyond the inner wall of theintestine during each injection, such as to prevent fluid delivery toodeep and/or too shallow into the intestinal wall. In some embodiments,distance D_(E) comprises a distance of less than or equal to 8 mm, suchas less than or equal to 6 mm, 5 mm, 4 mm, 3 mm or 2 mm.

In some embodiments, catheter 100 of FIG. 13 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 14, a side sectional view of a distal portion of acatheter comprising a functional assembly including an inner and outerballoon is illustrated, consistent with the present inventive concepts.Catheter 100 comprises shaft 110, functional assembly 130 (shown in itsexpanded state), and other components, such as one or more components ofsimilar construction and arrangement to those described hereabove inreference to catheter 100 of FIG. 1 or FIG. 2, such as one or moreconduits 111, some of which have been removed for illustrative clarity(two conduits 111 shown in FIG. 14). Catheter 100 can comprise bulboustip 115 on its distal end. Functional assembly 130 of FIG. 14 comprisesan outer balloon 136 a and an inner balloon 136 b. Catheter 100 can beconstructed and arranged such as to fill balloon 136 b with a firstfluid (e.g. a non-ablative gas) and fill the space between balloon 136 aand 136 b, space 146, with a second fluid (e.g. an ablative fluid suchas a fluid at an ablative temperature). Balloon 136 b can be filled viaconduit 111 b (partially expanding balloon 136 a), and space 146 can befilled via conduit 111 a (fully expanding balloon 136 a). Filling ofeither or both balloons can be accomplished with a console, such asconsole 200 described hereabove in reference to FIG. 1 or FIG. 2.

In some embodiments, balloon 136 b is configured to inflate rapidly witha gas, and space 146 is configured to inflate with a fluid such as aliquid or a gas. In these embodiments, a first fluid can be introducedinto space 146, such as a fluid at a cooling, warming or othernon-ablative temperature. In a second step, a fluid at an ablativetemperature is delivered into space 146, such as an ablative fluid thatis recirculated within space 146. In the dual-balloon configuration ofFIG. 14, the volume of ablative fluid is reduced (e.g. reduced by thevolume of balloon 136 a as compared to single balloon 136 embodimentsdescribed herein). In addition to rapid expansion, rapid radialcontraction of functional assembly 130 can be accomplished by rapidlywithdrawing gas from balloon 136 a, such as in an emergency situation.

In some embodiments, catheter 100 of FIG. 14 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 15, an end sectional view of a distal portion of acatheter comprising a functional assembly including two partialcircumferential balloons is illustrated, consistent with the presentinventive concepts. Catheter 100 comprises shaft 110, functionalassembly 130 (shown in its expanded state), and other components, suchas one or more components of similar construction and arrangement tothose described hereabove in reference to catheter 100 of FIG. 1 or FIG.2, such as one or more conduits 111 which have been removed forillustrative clarity. Catheter 100 can comprise bulbous tip 115 on itsdistal end (not shown). Functional assembly 130 of FIG. 15 comprises atreatment balloon 136 c configured to treat target tissue, and apositioning balloon 136 d configured to position treatment balloon 136 cagainst tissue. Catheter 100 can be constructed and arranged such as tofill balloon 136 c with a first fluid 135 c (e.g. an ablative fluid suchas a fluid at an ablative temperature), and fill balloon 136 d with asecond fluid 135 d (e.g. a non-ablative fluid such as a non-ablativegas). When both balloons 136 c and 136 d are fully inflated, functionalassembly 130 is fully expanded such as to contact intestinal walltissue.

When inflated, both balloon 136 c and balloon 136 d comprisecomplementary partial circumferential shapes, with a collective crosssection comprising a full or nearly-full circle. The outer surface ofballoon 136 c traverses arc ARC1 and the outer surface of balloon 136 dtraverses arc ARC2, such that arc ARC1 and arc ARC2 collectivelytraverse approximately 360°. In some embodiments, arc ARC1 of treatmentballoon 136 c traverses between 10° and 350° (i.e. balloon 136 dcorrespondingly traverses between 350° and 10°). Arc ARC1 of balloon 136c can be constructed and arranged to determine the circumferentialportion of an axial segment of intestinal tissue to be treated, such aswhen balloon 136 c is filled with ablative fluid. In these embodiments,balloon 136 c can be filled with neutralizing fluid prior to and/orafter being filled with ablative fluid, as described herein.

In some embodiments, functional assembly 130 comprises one or morefunctional elements, such as functional element 139 positioned in, onand/or within balloon 136 c and functional element 139 positioned in, onand/or within balloon 136 d. One or more functional elements 139 of FIG.15 can comprise a sensor, such as a sensor configured to produce asignal related to a condition of functional assembly 130 (e.g.temperature or pressure within one or more of balloons 136 c and/or 136d).

In some embodiments, catheter 100 of FIG. 15 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 16, a side sectional view of a distal portion of acatheter comprising a functional assembly including an inner chamber andan outer balloon is illustrated, consistent with the present inventiveconcepts. Catheter 100 comprises shaft 110, functional assembly 130(shown in its expanded state), and other components, such as one or morecomponents of similar construction and arrangement to those describedhereabove in reference to catheter 100 of FIG. 1 or FIG. 2, such as oneor more conduits 111 which have been removed for illustrative clarity(two conduits 111 shown in FIG. 16). Catheter 100 can comprise bulboustip 115 on its distal end. Functional assembly 130 of FIG. 16 comprisesan inflatable balloon, outer balloon 136 a which surrounds an innerchamber 136 b. Inner chamber 136 b can comprise an inflatable balloon aswell. Catheter 100 can comprise functional element 119 positioned in, onand/or within shaft 110 (e.g. proximate and/or within conduits 111 a or111 b), a functional element 139 positioned in, on and/or within balloon136 a, and/or a functional element 139 positioned in, on and/or withininner chamber 136 b. Functional elements 119 and/or 139 can eachcomprise one or more valves, such as a pressure-regulated valve,electronic valve, duckbill valve or other valve configured to modifyflow of fluid entering, exiting and/or within conduit 111 a, conduit 111b, balloon 136 a and/or inner chamber 136 b.

Catheter 100 can be constructed and arranged to fill inner chamber 136 bwith a fluid 135 b, and fill the space between balloon 136 a and innerchamber 136 b, space 146, with a fluid 135 a. Inner chamber 136 b can befilled via a lumen of shaft 110, conduit 111 b (partially expandingballoon 136 a), and space 146 can be filled via a separate lumen ofshaft 110, conduit 111 a (fully expanding balloon 136 a). Filling ofeither or both balloons can be accomplished with a console, such asconsole 200 described hereabove in reference to FIG. 1 or FIG. 2.

In some embodiments, fluid 135 b (which fills inner chamber 136 b)comprises a fluid at an ablative temperature (i.e. a liquid or gas at atemperature sufficiently hot or sufficiently cold to ablate tissue).Fluid 135 a, which fills space 146 between balloon 136 a and innerchamber 136 b, can comprise fluid at a neutralizing temperature, roomtemperature, or other temperature. Fluid 135 a, once in place withinspace 146, can be heated or cryogenically chilled by fluid 135 bcontained within inner chamber 136 b (i.e. in a heat exchangearrangement), such that when balloon 136 a is in contact with tissue,ablation of target tissue can be performed, as described herein. Innerchamber 136 b can comprise a balloon with a convoluted, complex,radiator-like and/or other shape configured to increase the area of theouter surface of inner chamber 136 b in contact with space 146, such asto enhance heat exchange between the two (e.g. a shape similar to theshape shown in FIG. 16). Fluid 135 a in space 146 and/or fluid 135 bwithin balloon 136 can be recirculated prior to and/or during ablationof tissue, such as via one or more pumps of an attached console, such asvia one or more pumping assemblies 225 of console 200 describedhereabove in reference to FIG. 1.

In other embodiments, inner chamber 136 b is filled with fluid 135 b oranother material at a non-ablative temperature and/or inner chamber 136b otherwise simply occupies space (e.g. with or without inflation ofinner chamber 136 b) within balloon 136 a. In these embodiments, innerchamber 136 b can be configured such that ablative energy is notdelivered from inner chamber 136 b to space 146. In these embodiments,inner chamber 136 b can be constructed and arranged to significantlyreduce the amount of an ablative fluid 135 a that otherwise would berequired to fully expand balloon 136 a, such as when inner chamber 136 bcomprises a volume of at least 30%, 40% or 50% of the volume defined bythe outer surface of a fully expanded balloon 136 a. Alternatively oradditionally, inner chamber 136 b can comprise a volume and/or a shapeconfigured to improve flow dynamics of fluid 135 b within space 146,such as when space 146 is filled with a recirculating ablative fluid 135b. Fluid 135 a in space 146 and/or fluid 135 b within balloon 136 can berecirculated prior to and/or during ablation of tissue, such as via oneor more pumps of an attached console, such as via one or more pumpingassemblies 225 of console 200 described hereabove in reference to FIG.1.

In some embodiments, catheter 100 of FIG. 16 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIGS. 17A-B, two anatomical, side sectional views of adistal portion of a catheter comprising a functional assembly and atleast one stabilizing assembly are illustrated, consistent with thepresent inventive concepts. Catheter 100 comprises shaft 110, functionalassembly 130 (shown in its compacted state in FIG. 17A and in itsexpanded state in FIG. 17B), and other components, such as one or morecomponents of similar construction and arrangement to those describedhereabove in reference to catheter 100 of FIG. 1 or FIG. 2, such as oneor more conduits 111, some of which have been removed for illustrativeclarity (three conduits 111 shown in FIGS. 17A-B). Catheter 100 cancomprise bulbous tip 115 on its distal end. Functional assembly 130 cancomprise an inflatable balloon, balloon 136, which can be fluidlyattached to an inflation lumen or tube, such as the attached conduit 111c shown. Catheter 100 further comprises one or more stabilizingassemblies, such as the two stabilizing assemblies 143 a and 143 b shownin FIG. 17. Stabilizing assemblies 143 a and/or 143 b (singly orcollectively stabilizing assembly 143), can each comprise an expandableassembly positioned proximate functional assembly 130, such as at orwithin 0.5 cm, 1.0 cm, 2.0 cm, 3.0 cm or 5.0 cm of either end offunctional assembly 130. In some embodiments, a first stabilizingassembly 143 (e.g. stabilizing assembly 143 a as shown) is positionedproximal to functional assembly 130 and a second stabilizing assembly143 (e.g. stabilizing assembly 143 b as shown) is positioned distal tofunctional assembly 130. In some embodiments, functional assembly 130comprises a length between 1 cm and 4 cm, such as a length between 2 cmand 3 cm. In some embodiments, one or more stabilizing assemblies 143comprise a length between 0.5 cm and 6.0 cm, such as a length between1.0 cm and 4.0 cm.

Each stabilizing assembly 143 can comprise a radially expandable elementsuch as a radially expanding element selected from the group consistingof: an inflatable balloon; a radially expandable cage or stent; one ormore radially deployable arms; an expandable helix; an unfurlablecompacted coiled structure; an unfurlable sheet; an unfoldable compactedstructure; and combinations of one or more of these. Each stabilizingassembly 143 can be operably attached to a conduit, such as conduits 111a and 111 b shown, each comprising a lumen configured to inflate astabilizing assembly 143 with a fluid (e.g. a liquid or a gas), or alumen that slidingly receives a control rod configured to expand theassociated stabilizing assembly 143. Each stabilizing assembly 143 cancomprise one or more functional elements, such as functional elements139 shown.

In some embodiments, catheter 100 is constructed and arranged to firstexpand one or more stabilizing assemblies 143, such as to centerfunctional assembly 130 within a lumen of the intestine while functionalassembly 130 is in a compacted or partially expanded state (e.g. torelatively center functional assembly 130 within a lumen of theintestine to avoid undesired contact of functional assembly 130 with theinner wall of the intestine), as is shown in FIG. 17A. In theseembodiments, a pre-centered functional assembly 130 can subsequentlyexpand to make contact with the wall of the intestine, as shown in FIG.17B. The filling of a pre-centered functional assembly 130 can avoidundesired partial-contact ablations, undesired partial fluid deliveryelement insertion tissue expansions, and/or other undesired energy orfluid transfer that might occur in a partially expanded state offunctional assembly 130.

Conduit 111 c can be constructed and arranged to provide and/or modify(e.g. reduce) ablative energy from functional assembly 130, such as aconduit configured to provide to, modify and/or extract from functionalassembly 130 one or more of: fluid at an ablative temperature; RFenergy; sound energy such as ultrasound energy; light energy such aslaser light energy; and combinations of one or more of these. In FIG.17A, stabilizing assemblies 143 a and 143 b have been expanded, whilefunctional assembly 130 remains radially compacted. Functional assembly130 is positioned at an axial segment of the intestine in which amedical procedure is to be performed (e.g. a tissue expansion procedureand/or a tissue ablation procedure). In FIG. 17B, functional assembly130 has been radially expanded to contact the intestinal wall at thedesired location. A subsequent tissue expansion, tissue ablation orother step can be performed using functional assembly 130. In someembodiments, confirmation of proper location of functional assembly 130is performed (e.g. via a visualization device as described herein) priorto expansion and/or ablation of tissue.

In some embodiments, stabilizing assembly 143 a and/or 143 b comprise ananchor element configured to be translated independent of functionalassembly 130. In some embodiments, stabilizing assemblies 143 a and 143b are expanded to anchor within intestinal tissue, and stabilizingassembly 143 a and/or 143 b are translated to stretch a segment ofintestine (e.g. place an axial segment of the intestine in tension afterwhich functional assembly 130 can be used to treat and/or diagnosetissue between stabilizing assemblies 143 a and 143 b). In someembodiments, one or more stabilizing assemblies 143 are configured totreat tissue and/or diagnose tissue, such as to deliver fluid to expandtissue and/or to deliver energy to tissue (e.g. when a stabilizingassembly 143 is filled with ablative fluid).

In some embodiments, catheter 100 of FIG. 17 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 18, an anatomical, side sectional view of a distalportion of a catheter comprising a functional assembly configured toavoid unintended translation within the intestine is illustrated,consistent with the present inventive concepts. Catheter 100 comprisesshaft 110, functional assembly 130 (shown in its expanded state), andother components, such as one or more components of similar constructionand arrangement to those described hereabove in reference to catheter100 of FIG. 1 or FIG. 2, such as one or more conduits 111, some of whichhave been removed for illustrative clarity (two conduits 111 shown inFIG. 18). Catheter 100 can comprise bulbous tip 115 (not shown, but suchas is described herein) on its distal end. Functional assembly 130 cancomprise an inflatable balloon, balloon 136. Functional assembly 130 canbe constructed and arranged to avoid unintended translation, such as toavoid translation between a first procedural step and a secondprocedural step that are intended to be performed at the same location(e.g. a tissue expansion procedure and a tissue ablation procedure thatshould be performed at the same relative axial segment of theintestine).

In some embodiments, functional assembly 130 (e.g. balloon 136)comprises a shape constructed and arranged to anchor functional assembly130 to prevent or otherwise reduce (herein “prevent”) unintendedtranslation of functional assembly 130 within the intestine, such as thedog-bone shape shown in FIG. 18. Other non-tubular shapes and/or othermulti-diameter shapes can be employed to avoid unintended translation,such as a shape comprising two or more trapezoidal cross sections.During intended translation, functional assembly 130 can be fully orpartially compacted as described herein.

Alternatively or additionally, functional assembly 130 can comprise aport 137 positioned on an outer surface of functional assembly 130 andconstructed and arranged to anchor functional assembly 130 to preventunintended translation of functional assembly 130 within the intestine(e.g. anchor functional assembly 130). Each port 137 can be fluidlyattached to a conduit 111 e, which can be configured to apply a vacuumto port 137, such as to engage with intestinal wall tissue to prevent orotherwise limit translation. During intended translation, vacuum can beremoved from the one or more ports 137.

Alternatively or additionally, functional assembly 130 can comprise oneor more extending anchors, such as the two extending anchors 144 ashown. Anchors 144 a can be configured to frictionally engage intestinaltissue when functional assembly 130 is expanded. Anchors 144 a cancomprise a barb-like geometry that can be oriented to preventtranslation in one or more directions, such as to prevent movement offunctional assembly 130 proximally (i.e. to the left of the page), asshown in FIG. 18.

Alternatively or additionally, functional assembly 130 can comprise atethered anchor, such as anchor 144 b shown in FIG. 18. Anchor 144 b canbe deployed, such as via one or more conduits 111, not shown. Anchor 144b can comprise a grasping structure configured to provide sufficientretention force to prevent unintended translation of functional assembly130, but still be intentionally disengaged by an operator of catheter100. Anchor 144 b can be attached to distal end 132 of functionalassembly 130 as shown, such as to prevent migration of functionalassembly 130 proximally (i.e. to the left of the page). In someembodiments, anchor 144 b or a separate anchor is attached to theproximal end 131 of functional assembly 130, such as to preventmigration of functional assembly 130 distally (i.e. to the right of thepage).

Alternatively or additionally, functional assembly 130 can comprise acoating configured to anchor prevent or otherwise reduce unintendedtranslation of functional assembly 130. Functional assembly 130 cancomprise coating 147 positioned on at least a portion of thetissue-contacting surfaces of functional assembly 130. Coating 147 cancomprise a coating and/or a surface treatment configured to enhancefrictional engagement of functional assembly 130 with tissue.

In some embodiments, catheter 100 of FIG. 18 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 19, an anatomical, side sectional view of a distalportion of a system and catheter comprising a functional assemblyincluding one or more reflective surfaces is illustrated, consistentwith the present inventive concepts. System 10 comprises catheter 100and a camera device, such as endoscope 50 a comprising camera 52.Catheter 100 has been advanced into an intestine, alongside endoscope 50a, to a desired axial segment of the intestine, to perform a medicalprocedure. In some embodiments, catheter 100 is introduced through aworking channel of endoscope 50 a, through a sheath and/or over aguidewire, as has been described herein. System 10 can comprise one ormore other components, such as console 200 and other components notshown, but similar to those described hereabove in reference to system10 of FIG. 1 or system 10 of FIG. 2. Catheter 100 comprises shaft 110,functional assembly 130 (shown in its expanded state), and othercomponents, such as one or more components of similar construction andarrangement to those described hereabove in reference to catheter 100 ofFIG. 1 or FIG. 2, such as one or more conduits 111, some of which havebeen removed for illustrative clarity (one conduit 111 shown in FIG.19). Catheter 100 can comprise bulbous tip 115 on its distal end.Functional assembly 130 can comprise an inflatable balloon, balloon 136,which can be fluidly attached to an inflation lumen, such as conduit 111shown.

Endoscope 50 a comprises camera 52 which provides a view distal to andalong the axis of the distal portion of endoscope 50 a. Catheter 100 cancomprise one or more reflectors, such as a reflector comprising areflective fluid (e.g. a reflective fluid positioned within balloon 136)and/or a reflective surface. Functional assembly 130 and/or anotherportion of catheter 100 can comprise a reflector selected from the groupconsisting of: mirror; folding mirror; foil-coated mylar portion; chrometape; acrylic mirror; and combinations of one or more of these. Forexample, functional assembly 130 can comprise one or more reflectivesurfaces, such as one or more of reflective surfaces 148 a, 148 b, 148 cand/or 148 d (singly or collectively reflective surface 148). Eachreflective surface 148 can comprise a flexible portion and/or a rigidportion, such as a reflective surface 148 comprising at least a flexibleportion positioned on, in and/or within functional assembly 130. Eachreflective surface 148 is positioned to be viewed by camera 52, andprovide a reflective image of intestinal tissue or a portion of system10 that otherwise might not be viewed by camera 52. Each reflectivesurface 148 can be positioned on a tapered portion of functionalassembly 130, such as at taper angles T_(A), T_(B), T_(c) and/or T_(D),respectively. Each reflective surface 148 can comprise a portion ofballoon 136. A reflective surface 148 can be positioned on a proximalportion of functional assembly 130, such as when the proximal portion offunctional assembly 130 comprises a geometry selected from the groupconsisting of: flat surface; convex surface; pyramid shaped surface; andcombinations of one or more of these. Reflective surfaces 148 a and 148b can be configured to provide an image of tissue or objects proximal tothe proximal end of functional assembly 130, such as tissue or objectsproximal to camera 52 and/or otherwise are outside of the field of viewof camera 52. Reflective surfaces 148 c and 148 d can be configured toprovide an image of tissue or objects proximal to the distal end offunctional assembly 130, or any tissue or objects proximal to the distalend of functional assembly 130. Functional assembly 130 can beconfigured to expand tissue and/or ablate tissue, such as a tissueexpansion or ablation involving use of an image provided by a reflectivesurface 148.

In some embodiments, one or more reflective surfaces 148 are positionedsuch that camera 52 views non-target tissue, such as viewing ofnon-target tissue such as the ampulla of Vater or other non-targettissue as described herein, that is viewed prior to and/or during anablation step.

In some embodiments, system 10 of FIG. 19 comprises one or more sensors,such as one or more functional elements 109, 119, 139, 209, 229 and/or309 described hereabove in reference to FIG. 1, that have beenconfigured as a sensor. These one or more sensors can be configured toprovide a signal, such as a signal used to adjust one or more console200 settings (e.g. console settings 201) of the present inventiveconcepts. In some embodiments, functional assembly 130 comprises one ormore functional elements, such as functional element 139 a, 139 b and/or139 c described hereabove in reference to FIG. 1, such as a functionalelement constructed and arranged to perform a therapeutic and/ordiagnostic medical procedure, as described herein.

Referring now to FIG. 20, a side sectional view of a distal portion of acatheter comprising a functional assembly attached to at least two fluidconduits is illustrated, consistent with the present inventive concepts.Catheter 100 comprises shaft 110, functional assembly 130 (shown in itsexpanded state), and other components, such as one or more components ofsimilar construction and arrangement to those described hereabove inreference to catheter 100 of FIG. 1 or FIG. 2, such as one or moreconduits 111, some of which have been removed for illustrative clarity(two conduits 111 shown in FIG. 20). Catheter 100 can comprise bulboustip 115 on its distal end. Functional assembly 130 can comprise aninflatable balloon, balloon 136 shown. Balloon 136 is fluidly attachedto a first fluid handling conduit, conduit 111 f, and a second fluidhandling conduit, conduit 111 g. Catheter 100 can be constructed andarranged to fill balloon 136 with fluid and/or evacuate balloon 136 offluid with both conduit 111 f and conduit 111 g, fills and/orevacuations with each conduit performed sequentially and/orsimultaneously, singly and/or collectively.

In some embodiments, catheter 100 is constructed and arranged to filland/or evacuate balloon 136 with conduits 111 f and conduit 111 gsimultaneously to reduce the fill and/or evacuation time that wouldresult with a single conduit 111. In some embodiments, catheter 100 isconstructed and arranged to switch from filling or evacuating with asingle conduit 111 to filling or evacuating, respectively, using atleast two conduits 111, when an undesired condition occurs (e.g. when anundesired condition is detected by an operator and/or automatically bysystem 10). In these embodiments, functional element 139 b can comprisea sensor configured to detect the undesired condition, such as a sensorconfigured to detect an occlusion (e.g. a pressure sensor or a flowsensor), a sensor configured to detect a leak (e.g. a fluid detector ora pressure sensor), a sensor configured to detect gas (e.g. undesiredgas) in a conduit 111, or combinations of one or more of these.Information from the sensor-based functional element 139 b can be usedto adjust flow of fluid, such as to modify (e.g. stop and/or reverse)flow of fluid after detection of a leak or occlusion, and/or to begindelivery of a second fluid (e.g. a neutralizing fluid) after detectionof a leak. In some embodiments, after detection of a leak or occlusionby a functional element 139 b, fluid can be delivered and/or extractedby two conduits 111 simultaneously.

In some embodiments, functional element 119 comprises a heating orcooling element configured to modify and/or control the temperature offluid entering balloon 136 via conduit 111 g. In these embodiments, oneor more conduits 111 can be fluidly connected to balloon 136, such asone or both of conduits 111 f and/or 111 g.

In some embodiments, functional assembly 130 further comprises one ormore functional elements 139 positioned on, in and/or within balloon136, such as multiple functional elements 139 equally separated along acircumference of balloon 136 (e.g. three elements spaced approximately120° apart). Each functional element 139 can span a length of balloon136 (e.g. as shown with dotted lines), or a portion of the length ofballoon 136. In some embodiments, functional element 139 can comprise aninsulating element configured to prevent or at least limit a transfer ofenergy (e.g. thermal energy) from functional assembly 130 to tissuelocations proximate each functional element 139. Treatment of an axialsegment of tissue that is less than 360° can be accomplished, forexample a near 360° segment of treated tissue with one or more axiallines of non-ablated tissue corresponding to the position of one or morefunctional elements 139. In some embodiments, treatment of less than360° of an axial segment is performed to reduce adverse effects, such asto reduce the likelihood of stricture formation. In some embodiments,functional element 139 is both an insulator as well as a fluid deliveryelement (e.g. fluid delivery element 139 c described herein). In theseembodiments, functional element 139 can comprise a port (e.g. port 137or other vacuum port), through which a needle or other fluid deliveryelement 139 c can translate or otherwise engage tissue for fluiddelivery into the tissue.

In some embodiments, catheter 100 of FIG. 20 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 21, a side sectional view of a distal portion of acatheter comprising a functional assembly including one or more lightdelivery elements is illustrated, consistent with the present inventiveconcepts. Catheter 100 comprises shaft 110, functional assembly 130(shown in its expanded state), and other components, such as one or morecomponents of similar construction and arrangement to those describedhereabove in reference to catheter 100 of FIG. 1 or FIG. 2, such as oneor more conduits 111, some of which have been removed for illustrativeclarity (one conduit 111 shown in FIG. 21). Catheter 100 can comprisebulbous tip 115 on its distal end. Functional assembly 130 can comprisean inflatable balloon, balloon 136, which can be fluidly attached to aninflation lumen, such as conduit 111 shown.

Functional assembly 130 can comprise one or more light deliveryelements, such as the three light delivery elements 149 shown in FIG.21. Light delivery elements 149 can be positioned anywhere on, in and/orwithin functional assembly 130, such as on a shaft 110 that passesthrough functional assembly 130 (also as shown). Functional assembly 130and light delivery elements 149 can be constructed and arranged toassist in the visualization of functional assembly 130, such as whenviewed by a camera device and/or simply viewed by an unassisted eye ofan operator of catheter 100. In some embodiments, light deliveryelements 149 deliver high intensity visible light which allows directvisualization of functional assembly 130 through the patient's skin(e.g. skin surrounding the abdominal wall). In some embodiments, one ormore light delivery elements 149 deliver non-visible light, such asinfrared light which can be visualized by an infrared (e.g. nearinfrared) or other non-visible light imaging device, such as imagingdevice 55 described hereabove in reference to FIG. 1. Alternatively oradditionally, light delivery element 149 can provide non-light energy,such as an element configured to produce a magnetic or electromagneticfield that can be detected by an external device to locate functionalassembly 130. Light delivery elements 149 can comprise one or more lightdelivery elements selected from the group consisting of: light; LED;optical component such as a lens, mirror or prism; a fluorescent agent(e.g. a fluorescent agent within and/or on functional assembly 130); andcombinations of one or more of these. Light delivery elements 149 can beoperably attached (e.g. electrically or optically) attached to a conduit(not shown but such as one or more conduits 111 described herein) whichis in turn attached to a source of power (e.g. one or more wiresattached to power of console 200) and/or light (e.g. one or more lightguides such as optical fibers attached to a light source of console200).

In some embodiments, catheter 100 of FIG. 21 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein.

Referring now to FIG. 22, a side view of a distal portion of a cathetercomprising a functional assembly comprising a first expanding elementand a second expanding element is illustrated, consistent with thepresent inventive concepts. Catheter 100 can comprise one or morecomponents of similar construction and arrangement to those describedhereabove in reference to catheter 100 of FIG. 1 or FIG. 2, such as oneor more conduits 111 which have been removed for illustrative clarity.Catheter 100 can comprise a shaft comprising an outer shaft 110 a and aninner shaft 110 b. Shaft 110 a comprises a lumen configured to slidinglyreceive shaft 110 b. Catheter 100 comprises a first functional assembly130 a mounted about a distal portion of shaft 110 a. Catheter 100further comprises a second functional assembly 130 b, positioned distalto functional assembly 130 a and mounted about a distal portion of shaft110 b. Functional assembly 130 a and/or functional assembly 130 b caneach be of similar construction and arrangement to functional assembly130 of FIG. 1, or functional assemblies 130, 25, 35 and/or 45 of FIG. 2.Catheter 100 can comprise bulbous tip 115 on its distal end.

Shaft 110 a and/or shaft 110 b can be operably attached to one or moretranslational controls (e g manual and/or mechanized controls on aproximal handle such as handle 102 of FIG. 1 or FIG. 2), such as totelescopically translate shaft 110 a relative to shaft 110 b. Thistranslation will accordingly change the distance between functionalassembly 130 a and functional assembly 130 b.

Functional assembly 130 a can comprise balloon 136 a and functionalassembly 130 b can comprise balloon 136 b. Each of functional assemblies130 a and 130 b can be configured to be radially expanded (each shown inFIG. 22 in an expanded state), such as via the delivery of one or morefluids into balloons 136 a and 136 b, respectively, such as via one ormore fluidly attached conduits 111 configured to deliver and withdrawinflation fluids, as described herein.

In some embodiments, functional assembly 130 a is constructed andarranged to expand tissue (e.g. one or more layers of tissue such assubmucosal tissue), such as when functional assembly 130 a comprises oneor more ports 137 and fluid delivery element 139 c (e.g. a curved needleas shown in FIG. 22 that can be fluidly attached to one or more conduitssupplying one or more injectates). In these embodiments, functionalassembly 130 a can be constructed and arranged as described hereabove inreference to functional assembly 130 of FIG. 1 or functional assembly 25of FIG. 2. Ports 137 can comprise two or more ports 137, such as threeports 137 distributed approximately 120° around a circumference offunctional assembly 130 a. Each port 137 can comprise a fluid deliveryelement 139 c configured to exit port 137 (as shown in FIG. 22), and/orremain within the associated port 137. Port 137 can be fluidly attachedto a vacuum source, such as via one or more fluidly attached conduits111, as described herein. In some embodiments, ports 137 and/or theassociated fluid delivery elements 139 c (e.g. a curved needle as shown,a straight needle, a nozzle, a fluid jet and the like), comprise atrajectory and/or are otherwise configured to deliver fluid and expandtissue distal to functional assembly 130 a, such as in a directiontowards functional assembly 130 b.

In some embodiments, functional assembly 130 b is constructed andarranged to ablate or otherwise treat target tissue, such as whenfunctional assembly 130 b is attached to a source of ablative energy asdescribed herein, such as one or more ablative fluids which aredelivered to and/or recirculated within functional assembly 130 b (e.g.via one or more fluidly attached conduits 111 configured to deliver andwithdraw ablative fluids, as described herein).

Functional assembly 130 a and functional assembly 130 b can compriseexpanded geometries configured to nest or otherwise mate with eachother, such as the concave shaped distal end of functional assembly 130a that comprises a size and shape configured to nest with the convexshaped proximal end of functional assembly 130 b.

In some embodiments, the distal portion of catheter 100 is positioned inan axial segment of intestinal tissue, and a tissue expansion (e.g.submucosal tissue expansion) is performed with balloon 136 africtionally engaging tissue. Subsequently, a tissue ablation isperformed using functional assembly 130 b, such as by first retractingor otherwise assuring that functional assembly 130 b is nested orotherwise in relative proximity to functional assembly 130 a, afterwhich the ablation energy can be delivered to tissue (e.g. balloon 136 bfilled with ablative fluid). In some embodiments, a tissue cooling orwarming procedure is performed prior to the delivery of the fluid at anablative temperature, as described herein.

In some embodiments, catheter 100 of FIG. 22 and/or a component attachedto catheter 100 comprises one or more sensors, such as functionalelements 119, 139 a (of functional assembly 130 a) and/or 139 b (offunctional assembly 130 b), that have been configured as a sensor. Insome embodiments, catheter 100 of FIG. 22 and/or a component attached tocatheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts.

Referring now to FIG. 23, a side sectional view of a distal portion of acatheter comprising an inner balloon configured to ablate and an outerballoon configured to position is illustrated, consistent with thepresent inventive concepts. Catheter 100 can comprise one or morecomponents of similar construction and arrangement to those describedhereabove in reference to catheter 100 of FIG. 1 or FIG. 2, such as oneor more conduits 111, some of which have been removed for illustrativeclarity (two conduits 111 shown in FIG. 23). Catheter 100 can comprise ashaft 110 comprising an outer shaft 110 a, an inner shaft 110 b and anextending shaft 110 c. Shaft 110 a comprises a lumen configured toslidingly receive shaft 110 b, and shaft 110 b comprises a lumen toslidingly receive shaft 110 c. Functional assembly 130 comprises outerballoon 136 a which is mounted about shaft 110 a and configured toposition (e.g. anchorably position) functional assembly 130 at a desiredaxial segment of intestinal tissue. Functional assembly 130 furthercomprises inner balloon 136 b, positioned within outer balloon 136 a,and mounted about shaft 110 b. Catheter 100 can comprise bulbous tip 115on its distal end. Catheter 100 can comprise functional element 119positioned in, on and/or within shaft 110 (e.g. proximate and/or withinconduits 111 a or 111 b), a functional element 139 positioned in, onand/or within outer balloon 136 a, and/or a functional element 139positioned in, on and/or within inner balloon 136 b. Functional elements119 and/or 139 can each comprise one or more valves, such as apressure-regulated valve, electronic valve, duckbill valve or othervalve configured to modify flow of fluid entering, exiting and/or withinconduit 111 a, conduit 111 b, outer balloon 136 a and/or inner balloon136 b.

Catheter 100 can be constructed and arranged to fill inner balloon 136 bwith a fluid 135 b, and fill outer balloon 136 a (e.g. fill the spacebetween outer balloon 136 a and inner balloon 136 b, space 146) withfluid 135 a. Inner balloon 136 b can be filled via a lumen of shaft 110b, conduit 111 b, and outer balloon 136 a can be filled via a lumen ofshaft 110 a, conduit 111 a. Filling of either or both balloons can beaccomplished with a console, such as console 200 described hereabove inreference to FIG. 1 or FIG. 2.

In some embodiments, fluid 135 b (which fills inner balloon 136 b)comprises a fluid at an ablative temperature (i.e. a liquid or gas at atemperature sufficiently hot or sufficiently cold to ablate tissue).Fluid 135 a which fills space 146 between outer balloon 136 a and innerballoon 136 b can comprise fluid at a neutralizing temperature, roomtemperature, or other temperature. In some embodiments, fluid 135 acomprises a gas.

Fluid 135 a in space 146 and/or fluid 135 b within inner balloon 136 bcan be recirculated prior to and/or during ablation of tissue, such asvia one or more pumps of an attached console, such as via one or morepumping assemblies 225 of console 200 described hereabove in referenceto FIG. 1.

Shaft 110 a, shaft 110 b and/or shaft 110 c can be operably attached toone or more translational controls or mechanical linkage assembly (e.g.a control on a proximal handle such as handle 102 of FIG. 1 or FIG. 2 ora mechanical linkage assembly of console 200), such as to telescopicallytranslate shaft 110 a relative to shaft 110 b, translate shaft 110 arelative to shaft 110 c, and/or translate shaft 110 b relative to shaft110 c. The position of inner balloon 136 b within outer balloon 136 acan be changed by translating inner shaft 110 b along shaft 110 c.

In some embodiments, outer balloon 136 a is inflated with fluid 135 asuch that outer balloon 136 a contacts the inner wall of an axialsegment of intestinal tissue. Subsequently, inner balloon 136 b isfilled with fluid 135 b (e.g. with fluid at a cooling or warmingtemperature, or fluid at an ablative temperature), expanding innerballoon 136 b to sufficiently contact the inner surface of outer balloon136 a, such that thermal energy can be transferred between inner balloon136 b and tissue proximate inner balloon 136 b (e.g. energy transferredthrough the contacting portion of outer balloon 136 a). In someembodiments, inner balloon 136 b is first filled with fluid at anon-ablative temperature (e.g. a cooled fluid configured to extract heatfrom tissue) and subsequently filled with fluid at an ablativetemperature (e.g. a heated fluid configured to ablate tissue). In someembodiments, after an ablative fluid is delivered to inner balloon 136 b(whether or not a non-ablative fluid was first delivered to innerballoon 136 b), a non-ablative fluid is subsequently delivered to innerballoon 136 b (e.g. to neutralize the effects of tissue ablation). Inthese various embodiments, neutralizing fluid, ablative fluid and/orother fluid can be recirculated within inner balloon 136 b, as describedherein.

As described above, inner balloon 136 b can be translated within outerballoon 136 a, such as by advancing and/or retracting shaft 110 b. Insome embodiments, outer balloon 136 a is inflated to frictionally engagean axial segment of intestinal tissue. Subsequently, inner balloon 136 bis positioned at a first location within outer balloon 136 a, and afirst ablation step is performed. Subsequently, inner balloon 136 b ispositioned at a second location within outer balloon 136 a (e.g. withoutrepositioning outer balloon 136 a), and a second ablation step isperformed. Additional similar repositioning and ablating steps can berepeated, such as to treat all or a portion of the length of theintestine contacted by outer balloon 136 a. In addition to introducingfluid at an ablative temperature to inner balloon 136 b, each ablationstep can include introducing a non-ablative fluid (e.g. a cooling fluid)prior to and/or after the delivery of the ablative fluid.

Alternative to the step-wise placement of inner balloon 136 b followedby a period of ablation, which can be repeated, catheter 100 can beconfigured to deliver ablative fluid into inner balloon 136 b and totreat target tissue while translating (continuously or intermittently)inner balloon 136 b within outer balloon 136 a, such as translationperformed at a rate sufficiently slow to ablate target tissue, butsufficiently fast to avoid adversely affecting non-target tissue. Insome embodiments, inner balloon 136 b is manually or automaticallyadvanced at an average rate of at least 1 mm/minute, such as a rate ofat least 2 mm/minute or 3 mm/minute. In some embodiments, inner balloon136 b is manually or automatically advanced at an average rate of lessthan 3 mm/second, such as a rate of less than 2 mm/second or 1mm/second.

In some embodiments, inner balloon 136 b treats target tissue withoutablative fluid, such as by delivering RF energy, light energy and/orother energy as described herein. In some embodiments, outer balloon 136a can comprise a fluid delivery element (such as fluid delivery element139 c described hereabove in reference to FIG. 1), which can beconstructed and arranged to expand tissue proximate outer balloon 136 a,such as during a tissue expansion procedure that occurs prior to one ormore ablation steps performed by inner balloon 136 b. In someembodiments, outer balloon 136 a comprises a length of at least 3 cm, atleast 4 cm, at least 5 cm, or at least 6 cm. In these embodiments, innerballoon 136 b can comprise a length of at least 0.5 cm, such as at least1.0 cm, 1.5 cm, 2.0 cm, 2.5 cm or 3.0 cm.

In some embodiments, catheter 100 of FIG. 23 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein, as described herein.

Referring now to FIG. 24, a side view of a distal portion of a cathetercomprising a functional assembly including a first expanding element anda second expanding element is illustrated, consistent with the presentinventive concepts. Catheter 100 can comprise one or more components ofsimilar construction and arrangement to those described hereabove inreference to catheter 100 of FIG. 1 or FIG. 2, such as one or moreconduits 111 which have been removed for illustrative clarity. Catheter100 can comprise a shaft comprising an outer shaft 110 a and an innershaft 110 b. Shaft 110 a comprises a lumen configured to slidinglyreceive shaft 110 b. Catheter 100 can comprise bulbous tip 115 on itsdistal end.

Catheter 100 of FIG. 24 comprises a first functional assembly 130 amounted about a distal portion of shaft 110 a. Catheter 100 furthercomprises a second functional assembly 130 b, positioned distal tofunctional assembly 130 a and mounted about a distal portion of shaft110 b. Functional assembly 130 a and/or functional assembly 130 b caneach be of similar construction and arrangement to functional assembly130 of FIG. 1, or functional assemblies 130, 25, 35 and/or 45 of FIG. 2.In some embodiments, one of functional assembly 130 a or 130 b comprisesan expandable element, such as an expandable element selected from thegroup consisting of: an inflatable balloon (e.g. inflatable balloon 136described herein); a radially expandable cage or stent; one or moreradially deployable arms; an expandable helix; an unfurlable compactedcoiled structure; an unfurlable sheet; an unfoldable compactedstructure; and combinations of one or more of these. In theseembodiments, relative translation of functional assemblies 130 a and 130b can be used to manipulate tissue, such as to place an axial segment ofintestinal tissue in tension.

Shaft 110 a and/or shaft 110 b can be operably attached to one or moretranslational controls or mechanical linkage assemblies (e.g. on aproximal handle such as handle 102 of FIG. 1 or FIG. 2 or a mechanicallinkage assembly of console 200), such as to telescopically translateshaft 110 a relative to shaft 110 b. This translation will accordinglychange the distance between functional assembly 130 a and functionalassembly 130 b.

Each of functional assemblies 130 a and 130 b can be configured to beradially expanded (each shown in FIG. 24 in an expanded state), such asvia the delivery of one or more fluids into functional assemblies 130 aand 130 b, such as via one or more fluidly attached conduits 111, notshown but configured to deliver and withdraw inflation fluids, asdescribed herein. Functional assembly 130 a and/or 130 b can compriseone or more functional elements 139 configured to perform a medicalprocedure, such as to deliver energy and/or fluid to tissue in atherapeutic medical procedure, as described herein.

In some embodiments, functional assembly 130 a and/or 130 b isconstructed and arranged to expand tissue, such as when the functionalassembly 130 comprises one or more fluid delivery elements (e.g. fluiddelivery element 139 c of FIG. 1) and optionally a tissue-engaging port(e.g. port 137 of FIG. 1) surrounding each fluid delivery element 139 cas described herein. In these embodiments, functional assembly 130 a canbe constructed and arranged as described hereabove in reference tofunctional assembly 130 of FIG. 1 or functional assembly 25 of FIG. 2.Alternatively or additionally, functional assembly 130 a and/or 130 bcan be constructed and arranged to deliver energy to tissue, such aswhen the functional assembly 130 is configured to receive ablative fluidor to deliver RF, light energy, sound energy and/or other energy totissue. In some embodiments, one of functional assembly 130 a or 130 bis configured to perform a tissue expansion step and the otherfunctional assembly 130 is configured to perform a tissue ablation step.In other embodiments, a first functional assembly 130 comprisingfunctional assembly 130 a or 130 b is configured to perform a tissueexpansion and/or ablation step and a second functional assembly 130comprising the other functional assembly is configured to provide ananchoring function, such as to stabilize the first functional assembly130.

In some embodiments, catheter 100 comprises one or more sensors, such asfunctional elements 119, 139 a (of functional assembly 130 a) and/or 139b (of functional assembly 130 b), that have been configured as a sensor.In some embodiments, catheter 100 of FIG. 24 and/or a component attachedto catheter 100 comprises one or more sensors, such as one or morefunctional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts.

Referring now to FIGS. 25A-C, anatomical, side sectional views of thedistal portion of a multiple expandable assembly catheter in a series ofsteps are illustrated, consistent with the present inventive concepts.Catheter 100 comprises shaft 110 and other components, such as one ormore components of similar construction and arrangement to thosedescribed hereabove in reference to catheter 100 of FIG. 1 or FIG. 2,such as one or more conduits 111 which have been removed forillustrative clarity. Catheter 100 can comprise bulbous tip 115 on itsdistal end. Catheter 100 comprises a functional assembly 130, positionedon a distal portion of catheter 100 (e.g. positioned on a distal portionof shaft 110), and comprising multiple expandable functional assemblies,such as two or more functional assemblies, such as the six functionalassemblies 130 a, 130 b, 130 c, 130 d, 130 e and 130 f shown (singly orcollectively functional assembly 130). Each functional assembly 130 canbe configured to radially expand and contract, such as a functionalassembly comprising an expandable element, such as an element selectedfrom the group consisting of: an inflatable balloon (e.g. inflatableballoon 136 as described herein); a radially expandable cage or stent;one or more radially deployable arms; an expandable helix; an unfurlablecompacted coiled structure; an unfurlable sheet; an unfoldable compactedstructure; and combinations of one or more of these. In someembodiments, a first functional assembly 130 comprises a first type ofexpandable element such as a balloon configured to be filled with fluid,and a second functional assembly 130 comprises a different type ofexpandable element, such as an expandable cage or stent. In someembodiments, each functional assembly 130 is operably attached to adifferent conduit 111, not shown but configured to allow independentradial expansion and contraction of each functional assembly 130 (e.g.individual conduits 111 comprising individual inflation lumens and/orindividual expansion control rods). Alternatively or additionally, twoor more functional assemblies 130 can be operably attached to a singleconduit 111, such as two or more functional assemblies 130 comprising aballoon connected to a single inflation lumen configured to expand (e.g.inflate) and/or compact (e.g. deflate) the two or more functionalassemblies 130 relatively simultaneously or at least in a mannerdependent on the other.

Each functional assembly 130 can comprise a functional element 139, suchas a functional element comprising one or more of: a sensor; atransducer; a tissue treatment element; a fluid delivery element such asa needle; and combinations of one or more of these.

In some embodiments, one or more functional assemblies 130 is configuredto treat and/or diagnose tissue, such as a functional assembly 130configured to expand tissue and/or ablate tissue. In these embodiments,one or more different functional assemblies 130 can be configured toprovide an anchoring force configured to prevent unintended translationof the distal portion of catheter 100. For example, a series offunctional assemblies 130 can comprise alternating tissue treatmentfunctional assemblies 130 and/or tissue diagnosis functional assemblies130 and anchoring functional assemblies 130.

One or more of functional assemblies 130 a-f can be configured to treatand/or diagnose tissue simultaneously or sequentially. As shown in FIG.25A, all functional assemblies 130 a-f can be in an expanded statesimultaneously (e.g. via a simultaneous or non-simultaneous expansion).Each functional assembly 130 can be configured to ablate or expandtissue simultaneously with one or more other functional assemblies 130.In some embodiments, a first set of functional assemblies 130 can beconfigured to receive ablative fluid to ablate tissue (e.g. a hotfluid), and a different set of functional assemblies 130 (e.g.positioned in between the ablating functional elements in an alternatingpattern) configured to receive a neutralizing fluid (e.g. a coolingfluid) to limit or otherwise control the amount of tissue ablated by theablating functional assemblies 130.

In some embodiments, one set of functional assemblies (e.g. functionalassemblies 130 a, 130 c and 130 e as shown) are expanded, and a secondset of functional assemblies (e.g. functional assemblies 130 b, 130 dand 130 f) are unexpanded or partially expanded (as shown). Anycombination of functional assemblies 130 can be operated in fullyexpanded, partially expanded or contracted states, in any configuration,such as is shown in FIG. 25C in which a series of three borderingfunctional assemblies, 130 a, 130 b and 130 c, are expanded, and aseries of three bordering functional assemblies, 130 d, 130 e and 130 fare partially expanded.

In some embodiments, a first set of one or more functional assemblies130 are expanded to anchor the distal portion of catheter 100, while asecond set of one or more functional assemblies 130 remain partiallyexpanded or contracted. In these embodiments, the expanded set offunctional assemblies 130 can be configured to perform a medicalprocedure such as a tissue expansion and/or ablation procedure.Alternatively, the set of unexpanded functional assemblies 130 can beexpanded (e.g. to contact the intestinal wall), and one or morefunctional assemblies 130 of either set used to perform the medicalprocedure.

Referring now to FIG. 26, a side sectional view of an anchorableguidewire is illustrated, consistent with the present inventiveconcepts. Guidewire 60′ comprises shaft 61 and expandable element 62positioned on the distal end or a distal portion of shaft 61. Expandableelement 62 is constructed and arranged to frictionally engage the innerwalls of a segment of the intestine, such as to provide an anchoringforce when one or more devices, such as the catheter of the presentinventive concepts (e.g. catheter 100 of FIG. 1 or catheters 100, 20, 30and/or 40 of FIG. 2) is advanced over guidewire 60′. In someembodiments, expandable element 62 is configured to expand to a diameterbetween 1.0 cm and 10.0 cm. Expandable element 62 can comprise anexpandable element selected from the group consisting of: an inflatableballoon; a radially expandable cage or stent; one or more radiallydeployable arms; an expandable helix; an unfurlable compacted coiledstructure; an unfurlable sheet; an unfoldable compacted structure; andcombinations of one or more of these. Shaft 61 and expandable element 62(in its radially compacted state) comprise a diameter configured to beslidingly received by one or more guidewire lumens, such as lumen 116 ofcatheter 100 described hereabove in reference to FIG. 1.

Guidewire 60′ comprises an assembly configured to expand and contractexpandable element 62, such as valve assembly 63. Valve assembly 63comprises a diameter configured to be slidingly received by one or moreguidewire lumens, such as lumen 116 of catheter 100 described hereabovein reference to FIG. 1. In some embodiments, valve assembly 63 ispositioned within the walls of shaft 61 or valve assembly 63 comprises asimilar diameter to shaft 61, such as to allow guidewire 60′ to passthrough an appropriate lumen of a device without excessive translationforce being required. In some embodiments, valve assembly 63 is ofsimilar construction and arrangement to that described in U.S. Pat. No.6,325,777.

In some embodiments, expandable element 62 comprises an inflatablestructure, such as an inflatable balloon (e.g. a compliant balloon or anon-compliant balloon) which is fluidly attached to valve assembly 63 bylumen 64 which travels between expandable element 62 and the proximalend of shaft 61. Valve assembly 63 is configured to allow a fluid suchas a gas (e.g. air) or a liquid (e.g. saline) to be introduced intoexpandable element 62 via valve assembly 63 and lumen 64. Valve assembly63 can be further configured to maintain expandable element 62 in aninflated state (inflated state shown in FIG. 26).

Referring additionally to FIG. 26A, a side sectional view of theproximal portion of guidewire 60′ is illustrated, with expansion tool 65attached about valve assembly 63, consistent with the present inventiveconcepts. Expansion tool 65 is configured to slidingly engage valveassembly 63, and to cause expandable element 62 to expand (e.g. toexpand to frictionally engage an inner wall portion of the intestine)and/or to contract (e.g. to disengage from an inner wall portion of theintestine). In some embodiments, expansion tool 65 comprises a mechanismactivation element, such as coil 66 which can be attached to electricalpower (not shown but such as a battery of expansion tool 65) to create amagnetic field which opens a magnetically activated valve assembly 63,such that fluid can be delivered into and/or extracted from expansionelement 62. When tool 65 is removed from guidewire 60′ (i.e. moved awayfrom valve assembly 63), valve assembly 63 can close, maintainingexpandable element 62 in the expanded or compacted state it was in priorto the removal of tool 65.

Referring now to FIG. 27, a medical device shaft comprising a taperedprofile is illustrated, consistent with the present inventive concepts.Shaft 110′ comprises a tapered outer wall whose wall thickness decreasesalong its length, such as to be more flexible as it approaches itsdistal end (e.g. to the right of the page). One or more conduits 111 ofthe present inventive concepts are positioned in, on and/or within shaft110′ (three shown in FIG. 27). Alternatively or additionally, shaft 110′can comprise multiple materials whose combination within an inner and/orouter wall changes along its length, such as to create a variablestiffness along its length, such as to be more flexible on a distalportion. Shaft 110′ can comprise a stiffness that changes relativelycontinuously, or in one or more discrete steps. Shaft 110′ can comprisea stiffness that changes along the majority of its length, or along oneor more discrete portions (e.g. at a distal portion or at amid-portion).

Shaft 110′ can comprise one or more functional elements 119, such as afunctional element 119 described hereabove in reference to FIG. 1 thathas been configured as a sensor. These one or more sensors can beconfigured to provide a signal, such as a signal used to adjust one ormore console 200 settings (e.g. console settings 201) of the presentinventive concepts.

Referring now to FIG. 28, a medical device shaft comprising a variedpitch braid is illustrated, consistent with the present inventiveconcepts. Shaft 110″ comprises a braided shaft, including braid filament117 within its outer wall. One or more conduits 111 of the presentinventive concepts are positioned in, on and/or within shaft 110″ (threeshown in FIG. 28). Braid filament 117 can comprise a metal filament(e.g. stainless steel filament) or a non-metal filament, (e.g. a plasticfilament). Shaft 110″ can comprise a braid whose pitch varies along itslength, such that the stiffness of shaft 110″ changes along its length,such as to become more flexible towards its distal end by decreasing thepitch (i.e. less turns per length) of braid filament 117, as shown inFIG. 28. Alternatively or additionally, one or more parameters of braidfilament 117 can be varied along the length of shaft 110″, such as itsmaterial, diameter or other parameter that would influence the stiffnessimparted by braid filament 117 upon shaft 110″. Shaft 110″ can comprisea stiffness that changes relatively continuously, or in one or morediscrete steps. Shaft 110″ can comprise a stiffness that changes alongthe majority of its length, or along one or more discrete portions (e.g.at a distal portion or at a mid-portion).

Shaft 110″ can comprise one or more functional elements 119, such as afunctional element 119 described hereabove in reference to FIG. 1 thathas been configured as a sensor. These one or more sensors can beconfigured to provide a signal, such as a signal used to adjust one ormore console 200 settings (e.g. console settings 201) of the presentinventive concepts.

Referring now to FIGS. 29A-D, a camera view of a series of steps forexpanding tissue and treating target tissue at a single axial segment ofintestine are illustrated, consistent with the present inventiveconcepts. A distal portion of catheter 100 is being viewed by a cameradevice (e.g. configured as a sensor of the present inventive concepts),such as an endoscopic camera such as a camera of endoscope 50 adescribed hereabove in reference to FIGS. 1, 2 and 19, and/or camera 52of FIG. 19. Catheter 100 comprises shaft 110, functional assembly 130(shown in its expanded state), and other components, such as one or morecomponents of similar construction and arrangement to those describedhereabove in reference to catheter 100 of FIG. 1 or FIG. 2, such as oneor more conduits 111 which have been removed for illustrative clarity.Functional assembly 130 can comprise an expandable element, such asballoon 136 shown. Functional assembly 130 of catheter 100 has beenintroduced into the intestine, such as by being inserted via one or moreof: through a working channel of an endoscope (e.g. the endoscopeproducing the camera view); over a guidewire; inserted alongside anendoscope (e.g. over a guidewire); through a sheath attached to orindependent of an endoscope (e.g. over a guidewire); through alaparoscopic port (e.g. over a guidewire); and/or through any bodyintroduction device.

Functional assembly 130 comprises a distal wall (e.g. distal wall 132shown in the camera view), and a proximal wall (e.g. proximal wall 131described hereabove in reference to FIGS. 6A, 6B and 18), and aside-wall portion therebetween. Functional assembly 130 of catheter 100has been inserted into an axial segment of the intestine, and inflatedsuch that a tissue-contacting portion of balloon 136 is in substantialcontact with the inner wall of the axial segment of the intestine (i.e.all portions of functional assembly 130 shown in the camera view ofFIGS. 29A-D except for distal wall 132). The image provided by thecamera is looking through at least a portion of the proximal wall offunctional assembly 130 (e.g. an endoscope or other camera device hasbeen advanced to a location relatively proximate the proximal wall offunctional assembly 130). At least the proximal wall of functionalassembly 130 is constructed of materials to be transparent, or at leastrelatively transparent (hereinafter “transparent”) to the camera view,such as a clear material transparent with respect to the camera beingused (e.g. transparent to visible light used by a visible light camera,transparent to infrared light used by an infrared camera, transparent toultrasound waves as used by an ultrasound imager and/or transparent toradiation used by a radiation-based camera). At least one or moreportions of the tissue-contacting surfaces (e.g. portions of theside-wall) of functional assembly 130 can also be transparent to thecamera view, such as is shown in FIG. 29D, such as to view the tissue incontact with functional assembly 130 during a therapeutic or diagnosticprocedure. In some embodiments, at least a portion of the distal wall istransparent. For example, system 10 can be configured to detect a changeof the tissue (e.g. a color change) and/or a change to a materialdelivered into the tissue, such as injectate 221 described herein, andto adjust one or more console settings 201 based on the color change orother image information (e.g. a console setting related to an injectatedelivery parameter during tissue expansion and/or an energy deliveryparameter during tissue ablation).

In some embodiments, functional assembly 130 is configured to bothexpand tissue and ablate tissue, such that a single functional assembly130 can be positioned, anchored, and complete the tissue expansion stepsdescribed herebelow in reference to FIGS. 29A-B, and subsequently (whileremaining anchored in the same axial location of intestine) complete thetissue ablation steps described herebelow in reference to FIGS. 29C-D.Functional assembly 130 can be anchored throughout the tissue expansionand tissue treatment steps by maintaining sufficient force against thelumen wall, such as by sufficient expansion of functional assembly 130and/or by other anchoring means as described herein.

In other embodiments, a first functional assembly 130 is configured toexpand tissue, and a second functional assembly 130 is configured totreat tissue. In these embodiments, the first functional assembly ispositioned, anchored, and used to complete the tissue expansion stepsdescribed herebelow in reference to FIGS. 29A-B. Subsequently, the firstfunctional assembly 130 is moved away from the axial segment, and asecond functional assembly 130 (e.g. positioned on the same catheter 100or a second catheter 100) is positioned in the same axial segment,anchored, and used to complete the tissue ablation steps describedherebelow in reference to FIGS. 29C-D.

In FIG. 29A, a tissue expansion step has been initiated, such as atissue expansion step in which one or more needles or other fluiddelivery elements (e.g. three equally spaced fluid delivery elements 139c of FIG. 1) are delivering fluid into tissue (e.g. submucosal tissue ofthe intestine). As shown in FIG. 29A, certain areas of tissue have beenexpanded, areas of tissue T_(EXP), while other areas in contact with thetissue-contacting portions (e.g. sidewalls) of functional assembly 130,T_(NOT EXP) are unexpanded (e.g. yet to be expanded). In someembodiments, the visual feedback of the camera view of FIG. 29A isprovided to an operator (e.g. via a display of console 200 or endoscope50 a described hereabove in reference to FIG. 1), such that the operatorcan continue fluid delivery until all desired tissue is expanded.Alternatively or additionally, system 10 can be configured to assesscompleteness of tissue expansion, such as to continue or otherwiseadjust fluid delivery (e.g. automatically), and/or notify the operatorof a desire to continue fluid delivery, based on the visual feedback. Insome embodiments, the fluid delivered (e.g. injectate 221 of FIG. 1)comprises visualizable material configured to be visualized, to enhancevisualization of expanded tissue and/or to identify an adverse situationsuch as delivered fluid leaking into the intestinal lumen (e.g. versus asubmucosal layer of tissue).

In FIG. 29B, relatively all of the tissue desired to be expanded byfunctional assembly 130 has been expanded. In some embodiments,sufficient expansion of tissue is visually confirmed (e.g. an operatormanually confirms that all, a majority, or any sufficient amount of thetissue in contact with functional assembly 130 and potentially beyondfunctional assembly 130 has been expanded). This confirmation can beperformed prior to performing a subsequent step, such as an ablationstep. In some embodiments, system 10 is configured to confirm sufficienttissue expansion has been completed (e.g. automatically orsemi-automatically), such as via an image analysis algorithm, such asalgorithm 251 of controller 250 described hereabove in reference toFIG. 1. In some embodiments, visualizable or other material of injectate221 is detected by the camera device or one or more other sensors ofsystem 10, and algorithm 251 correlates the amount and/or location ofthe detected material to a level of tissue expansion.

In FIG. 29C, a target tissue ablation step has been subsequentlyinitiated, such as a target tissue ablation step in which energy isdelivered to tissue (e.g. via ablative fluid being introduced intofunctional assembly 130 and/or by delivery of RF of other energy intotissue by functional assembly 130). In some embodiments, the targettissue treated comprises mucosal tissue of the duodenum or otherintestinal mucosal tissue, such as to treat diabetes,hypercholesterolemia, and/or another patient disease or disorder. Asshown in FIG. 29C, certain areas of tissue have been treated, areas oftissue T_(TRTD), while other areas in contact with the tissue-contactingportions (e.g. sidewalls) of functional assembly 130 are simply expanded(T_(EXP) shown in FIG. 29C). In some embodiments, system 10 isconfigured to provide visual feedback of the camera view of FIG. 29C toan operator (e.g. via a display of console 200 or endoscope 50 adescribed hereabove in reference to FIG. 1), such that the operator cancontinue tissue ablation until all desired tissue is treated.Alternatively or additionally, system 10 can be configured to assesscompleteness of tissue ablation and to adjust tissue ablation consolesetting (e.g. automatically), based on the visual feedback. In someembodiments, ablated tissue is identified by a color change that occursduring ablation. Alternatively or additionally, system 10 can beconfigured to further differentiate ablated tissue, such as by detectinga color or other change to injectate 221 delivered in the tissueexpansion steps.

In FIG. 29D, relatively all of the tissue desired to be ablated byfunctional assembly 130 has been treated. In some embodiments,sufficient treatment of tissue is visually confirmed (e.g. an operatormanually confirms that all, a majority, or any sufficient amount of thetissue in contact with functional assembly 130 has been ablated orotherwise treated). This confirmation is performed prior to removingfunctional assembly 130 and/or repositioning functional assembly 130 ata different axial segment (e.g. when a medical procedure comprisesablating multiple axial segments, as described herein). In someembodiments, system 10 is configured to confirm sufficient tissueablation or other treatment has been completed (e.g. automatically orsemi-automatically), such as via an image analysis algorithm, such asalgorithm 251 of controller 250 described hereabove in reference toFIG. 1. In some embodiments, visualizable changes or other changes toinjectate 221 within tissue is detected by the camera device or one ormore other sensors of system 10, and algorithm 251 correlates the amountand/or location of the changed injectate 221 to a level of tissueablation.

Referring now to FIGS. 30A-B, side sectional views of a distal portionof a catheter comprising a tissue-engaging fluid delivery element areillustrated, consistent with the present inventive concepts. Catheter100 comprises shaft 110, functional assembly 130 (shown in its expandedstate), and other components, such as one or more components of similarconstruction and arrangement to those described hereabove in referenceto catheter 100 of FIG. 1 or FIG. 2, such as one or more conduits 111,some of which have been removed for illustrative clarity (three conduits111 shown in FIGS. 30A-B). Catheter 100 can comprise bulbous tip 115 onits distal end. Shaft 110 of FIGS. 30A-B comprises at least shafts 110a, 110 b and 110 d shown. Shaft 110 can comprise additional shafts, suchas a shaft 110 c not shown but constructed and arranged such that shafts110 a, 110 b and 110 c are separated by approximately 120°. Functionalassembly 130 can comprise an inflatable balloon, balloon 136, such as aballoon configured to expand upon receiving inflation fluid via a lumenor tube such as conduit 111 d positioned within shaft 110 d. Shafts 110a and 110 b each comprise a conduit 111 a and 111 b, respectively, suchas translatable hollow tubes configured to advance and retract and allowdelivery and/or extraction of fluid (e.g. simultaneously orsequentially). Functional assembly 130 comprises one or more guidingelements 137′ that are positioned on a tissue-contacting portion offunctional assembly 130, such as three ports 137 distributed 120° apartalong a circumference of balloon 136 (two shown in FIGS. 30A-B). Eachguiding element 137′ comprises a channel configured to slidingly receivea fluid delivery element 139 c′ and guide the associated fluid deliveryelement 139 c′ into tissue at a particular trajectory. Each guidingelement 137′ is attached to a translatable conduit (e.g. conduits 111 aand 111 b shown), which is configured to provide fluid to each fluiddelivery element 139 c′ (e.g. injectate 221 as described hereabove inreference to FIG. 1), as well as advance and retract fluid deliveryelement 139 c′ in and out of guiding element 137′, as has been describedherein. Each fluid delivery element 139 c′ can be configured to deliverfluid to expand tissue (e.g. submucosal tissue of the duodenum or otherintestinal submucosa).

Fluid delivery element 139 c′ can comprise a tissue-engaging geometry,such as the spiraled (e.g. cork-screw) geometry shown in FIG. 30B. Forexample, fluid delivery element 139 c′ can be resiliently biased in acork-screw, helical, zig-zag or other tissue-engaging geometry that canbe straightened, for example when constrained within a channel ofguiding element 137′ as shown in FIG. 30A, and transition to anon-linear, tissue-engaging geometry when unconstrained, for examplewhen exiting guiding element 137′. The tissue-engaging geometry shown inFIG. 30B can be used to provide a tissue retention force when fluiddelivery element 139 c′ is positioned into tissue, such as to preventundesired or unintended movement of fluid delivery element 139 c′ duringfluid delivery and/or between fluid delivery steps. The tissue-engaginggeometry shown in FIG. 30B can avoid a separate tissue retentionelement, such as vacuum-assisted port such as a vacuum-assisted port 137described hereabove in reference to FIG. 1.

In some embodiments, catheter 100 of FIGS. 30A-B and/or a componentattached to catheter 100 comprises one or more sensors, such as one ormore functional elements 109, 119, 139, 209, 229 and/or 309 describedhereabove in reference to FIG. 1, that have been configured as a sensor.These one or more sensors can be configured to provide a signal, such asa signal used to adjust one or more console 200 settings (e.g. consolesettings 201) of the present inventive concepts. In some embodiments,functional assembly 130 comprises one or more functional elements, suchas functional element 139 a, 139 b and/or 139 c described hereabove inreference to FIG. 1, such as a functional element constructed andarranged to perform a therapeutic and/or diagnostic medical procedure,as described herein, as described herein.

Referring now to FIG. 31, a medical device shaft comprising one or moreinsulating elements is illustrated, consistent with the presentinventive concepts. Shaft 110′″ comprises at least one insulatingelement, such as the two insulating elements 152 shown. One or moreconduits 111 of the present inventive concepts are positioned in, onand/or within shaft 110′″. Each insulating element 152 can comprise anelement configured to insulate one or more internal portions of shaft110′″ from the outer surface of shaft 110′″. In some embodiments, one ormore conduits 111 can include fluid at an ablative temperature, and oneor more insulating elements 152 comprise a thermally insulating layer ofshaft 110′″ configured to prevent the outer wall of shaft 110′″ fromundesirably damaging intestinal wall tissue and/or a separate device incontact with and/or otherwise in proximity to the outer surface of shaft110′″. In some embodiments, one or more insulating elements 152 compriseone or more materials that have low thermal conductivity, such as amaterial with a lower thermal conductivity than the outer wall of shaft110′″ and/or lower than the thermal conductivity of an outer wall of aconduit 111. In some embodiments, one or more insulating elements 152comprise a thermos construction including a reflective surface and a gap(e.g. air gap) configured to provide insulation. In some embodiments,two or more insulating elements 152 transport a recirculating fluidconfigured to prevent the outer surface of shaft 110′″ from reaching anundesired temperature.

Shaft 110′″ can comprise one or more functional elements 119, such as afunctional element 119 described hereabove in reference to FIG. 1 thathas been configured as a sensor. These one or more sensors can beconfigured to provide a signal, such as a signal used to adjust one ormore console 200 settings (e.g. console settings 201) of the presentinventive concepts.

Referring now to FIG. 32, an end sectional view of a system comprising acatheter with a non-circular cross section and a body introductiondevice with a circular cross section is illustrated, consistent with thepresent inventive concepts. System 10 comprises catheter 100 and a bodyintroduction device 50, such as endoscope 50 a described herein. Bodyintroduction device 50 can comprise one or more working channels, suchas lumens 51 and 54 shown, and/or it can include an imaging device, suchas camera 52 shown. System 10 can comprise one or more other components,such as console 200 and other components not shown, but similar to thosedescribed hereabove in reference to system 10 of FIG. 1 or system 10 ofFIG. 2. Catheter 100 comprises functional assembly 130 (not shown), andother components, such as one or more components of similar constructionand arrangement to those described hereabove in reference to catheter100 of FIG. 1 or FIG. 2, such as one or more conduits 111, some of whichhave been removed for illustrative clarity (three conduits 111 shown inFIG. 32). Catheter 100 can comprise bulbous tip 115 on its distal end.

Catheter 100 comprises shaft 110″″, which comprises an oval,kidney-shape or other non-circular cross sectional geometry (e.g. thekidney-shaped geometry shown in FIG. 32) configured to partiallysurround body introduction device 50, such that when shaft 110″″ isnested against body introduction device 50, the cumulative peripherydefined by both shaft 110″″ and body introduction device 50 can beinserted into a tube (e.g. an intestinal or other GI lumen) with asmaller diameter than would be possible with a circular geometry shaftof catheter 100 of the same cross sectional area as shaft 110″″.

In some embodiments, system 10 of FIG. 32 comprises one or more sensors,such as one or more functional elements 109, 119, 139, 209, 229 and/or309 described hereabove in reference to FIG. 1, that have beenconfigured as a sensor. These one or more sensors can be configured toprovide a signal, such as a signal used to adjust one or more console200 settings (e.g. console settings 201) of the present inventiveconcepts. In some embodiments, functional assembly 130 comprises one ormore functional elements, such as functional element 139 a, 139 b and/or139 c described hereabove in reference to FIG. 1, such as a functionalelement constructed and arranged to perform a therapeutic and/ordiagnostic medical procedure, as described herein.

Referring now to FIG. 33, an end sectional view of a system comprising acatheter with a functional assembly comprising a non-circular unexpandedcross section and a body introduction device with a circular crosssection is illustrated, consistent with the present inventive concepts.System 10 comprises catheter 100 and a body introduction device 50, suchas endoscope 50 a described herein. Body introduction device 50 cancomprise one or more working channels, such as lumens 51 and 54 shown,and/or it can include an imaging device, such as camera 52 shown. System10 can comprise one or more other components, such as console 200 andother components not shown, but similar to those described hereabove inreference to system 10 of FIG. 1 or system 10 of FIG. 2. Catheter 100can comprise one or more components of similar construction andarrangement to those described hereabove in reference to catheter 100 ofFIG. 1 or FIG. 2, such as one or more conduits 111, some of which havebeen removed for illustrative clarity (three conduits 111 shown in FIG.33). Catheter 100 can comprise bulbous tip 115 on its distal end.

Catheter 100 comprises shaft 110, upon which functional assembly 130′ ismounted (e.g. on a distal portion of shaft 110). When radiallycollapsed, functional assembly 130′ comprises an oval, kidney-shape orother non-circular cross sectional geometry (e.g. the kidney-shapedgeometry shown in FIG. 33) configured to partially surround bodyintroduction device 50, such that when shaft 110 and a radiallycollapsed functional assembly 130′ are nested against body introductiondevice 50. The cumulative periphery defined by radially collapsedfunctional assembly 130′, shaft 110 and body introduction device 50 canbe inserted into a tube (e.g. an intestinal or other GI lumen) with asmaller diameter than would be possible with a radially compactedfunctional assembly 130 with a circular geometry and the same crosssectional area as functional assembly 130′.

In some embodiments, system 10 of FIG. 33 comprises one or more sensors,such as one or more functional elements 109, 119, 139, 209, 229 and/or309 described hereabove in reference to FIG. 1, that have beenconfigured as a sensor. These one or more sensors can be configured toprovide a signal, such as a signal used to adjust one or more console200 settings (e.g. console settings 201) of the present inventiveconcepts. In some embodiments, functional assembly 130 comprises one ormore functional elements, such as functional element 139 a, 139 b and/or139 c described hereabove in reference to FIG. 1, such as a functionalelement constructed and arranged to perform a therapeutic and/ordiagnostic medical procedure, as described herein.

Referring now to FIG. 34, a method of performing a medical procedureincluding gathering sensor information is illustrated, consistent withthe present inventive concepts. The method of FIG. 34 will be describedusing the devices and components of system 10 and one or more catheters100 described hereabove in reference to one or more of FIGS. 1-25. InStep 3410, the distal portion of a catheter 100, including a functionalassembly 130, is inserted into the intestine of a patient, such as aninsertion through a body introduction device 50, such as an endoscope orsheath, or an insertion alongside a body introduction device 50. In someembodiments, catheter 100 is inserted over a guidewire 60. Catheter 100can be attached to console 200 of system 10. System 10 and/or catheter100 can comprise one or more sensors configured to produce a signal,such as a signal used to set and/or change one or more console settings201 of system 10.

In Step 3420, functional assembly 130 is positioned at an axial segmentof the intestine. Sensor information can be gathered and the intestinallocation selected to position functional assembly 130 can be based onthe sensor information. Sensor information can be gathered by one ormore sensors of system 10, such as one or more functional elements 109,119, 139, 209, 229 and/or 309 described hereabove that have beenconfigured as a sensor.

In Step 3430, functional assembly 130 is activated and/or adjusted.Sensor information can be gathered, and functional assembly 130 can beactivated and/or adjusted based on the gathered sensor information.Sensor information can be gathered by one or more sensors of system 10,such as one or more functional elements 109, 119, 139, 209, 229 and/or309 described hereabove that have been configured as a sensor. In someembodiments, catheter 100 is activated and/or adjusted based on thesensor information. In some embodiments, activation of functionalassembly 130 comprises initiation of a function selected from the groupconsisting of: delivering fluid to tissue (e.g. delivering injectate 221to submucosal tissue or other tissue); delivering energy to tissue (e.g.delivering thermal energy to tissue from an ablative fluid or deliveringelectromagnetic energy such as RF energy to tissue) to treat targettissue; cooling and/or warming tissue (e.g. cooling and/or warmingperformed prior to and/or after a heat ablation or cryogenic ablation,respectively); performing a therapeutic procedure on tissue; performinga diagnostic procedure on tissue; and combinations of one or more ofthese. After initial activation, adjustment of functional assembly 130can comprise a modification selected from the group consisting of:adjustment of fluid delivery to tissue (e.g. adjustment of fluiddelivery rate from fluid delivery element 139 c or adjustment ofpressure within functional assembly 130); adjustment of energy deliveryto tissue (adjustment of temperature of ablative fluid within functionalassembly 130, adjustment of flow rate of fluid being delivered to and/orextracted from functional assembly 130, adjustment of pressure withinfunctional assembly 130, and/or adjustment of contact of functionalassembly 130 with tissue); adjustment of a therapeutic procedureparameter; adjustment of a diagnostic procedure parameter; adjustment offluid withdrawn from functional assembly 130; and combinations of one ormore of these.

In Step 3440, a check of procedure completeness is performed, eithermanually by an operator of system 10 and/or automatically orsemi-automatically by system 10 (e.g. via algorithm 251 of console 200).If incomplete, Step 3420 can be performed again, such as to repositionfunctional assembly 130 in a different (e.g. second) axial segment,after which Step 3430 can be performed in the different axial segment.Alternatively, if the procedure is determined to be incomplete, Step3430 can be repeated in the same axial segment (e.g. without therepositioning of Step 3420). If during Step 3440 it is determined theprocedure is complete, Step 3450 can be performed in which catheter 100is removed from the patient.

In some embodiments, Step 3430 comprises the performance of two medicalsteps, such as a first step involving tissue expansion and a second stepinvolving tissue ablation. In these embodiments, the first and secondsteps can be performed by a single functional assembly 130, such as afunctional assembly 130 configured to expand tissue (e.g. via a fluiddelivery element 139 c) and ablate tissue (e.g. via a functional element139 a). Alternatively, the first step can be performed by a firstfunctional assembly 130 and the second step performed by a secondfunctional assembly 130. The first and second functional assemblies canbe included in a single catheter 100, or on separate catheters 100. Inthese two functional assembly 130 embodiments, STEP 3420 (positioning offunctional assembly 130) can be repeated for each functional assembly130. Each functional assembly 130 and catheter 100 can comprise one ormore sensors configured to provide a signal to perform the positioningof Step 3420 and/or the activation and/or adjustment of Step 3430.

In some embodiments, Steps 3420 and 3430 are repeated two or more times,such as to treat a cumulative axial length of intestinal tissue of atleast 6 cm, such as at least 9 cm, such as when performing a duodenalmucosal ablation procedure of the present inventive concepts to treatdiabetes. In these embodiments, functional assembly 130 can beconstructed and arranged to treat a near full circumferential (e.g.between 320° and 360°) axial segment of mucosal tissue in each ablationstep. In these embodiments, each ablation step can be preceded by atissue expansion step (e.g. a submucosal tissue expansion step), such asto expand a near full circumferential (e.g. between 320° and 360°) axialsegment of submucosal tissue, such as to create a safety margin oftissue for the subsequent ablation step.

Referring now to FIG. 35, a method of performing a medical procedureincluding performing a tissue expansion with a functional assembly, andtreating target tissue with the same or a different functional assemblyis illustrated, consistent with the present inventive concepts. Themethod of FIG. 35 will be described using the devices and components ofsystem 10 and one or more catheters 100 described hereabove in referenceto one or more of FIGS. 1-25. In Step 3510, the distal portion of acatheter 100, including a functional assembly 130, is inserted into theintestine of a patient, such as an insertion through a body introductiondevice 50, such as an endoscope or sheath, or an insertion alongside abody introduction device 50. In some embodiments, catheter 100 isinserted over a guidewire 60. Catheter 100 can be attached to console200 of system 10. System 10 and/or catheter 100 can comprise one or moresensors configured to produce a signal, such as a signal used to setand/or change one or more console settings 201 of system 10.

In Step 3520, a first functional assembly 130 is positioned in theintestine (e.g. in the duodenum), and one or more layers of a firstaxial segment of intestinal tissue (e.g. submucosal tissue) is expanded.Tissue expansion can comprise expansion of a near full circumferential(e.g. between 320° and 360°) layer of tissue, and can be accomplished byone or more fluid delivery elements 139 c delivering injectate 221supplied by console 200 into one or more tissue locations (e.g. 3 tissuelocations simultaneously or sequentially without repositioningfunctional assembly 130).

In Step 3530, a second functional assembly 130 is positioned in alocation similar to (e.g. within) the first axial segment of expandedtissue. The first and second functional assemblies 130 can be includedon a single catheter 100 (e.g. in two different locations on shaft 110),or on two different catheters 100.

In Step 3540, a confirmation of proper placement can be performed (e.g.a visual examination that all sufficient tissue in contact with thesecond functional assembly 130 has been expanded). If improper placementis identified, the second functional assembly 130 can be repositioned inStep 3550 and/or the procedure can be aborted.

In Step 3560, the second functional assembly 130 is anchored in place,such as by expanding second functional assembly 130, and/or deployingone or more anchoring mechanisms as described herein.

In Step 3570, the second functional assembly 130 is activated to treat(e.g. ablate tissue) proximate second functional assembly 130. Theanchoring previously performed ensures that the treatment is performedin an area of expanded tissue (e.g. expanded submucosal tissue), such asto create a safety margin of tissue in all locations receiving energy orother treatment from second functional assembly 130 during the entiretreatment. For example, the anchoring performed prevents unknown orotherwise unintended translation of the second functional assembly 130prior to and/or during the treatment of Step 3570. Anchoring offunctional assembly 130 can be performed a single time or multipletimes, and can be maintained during any or all of the Steps 3510 through3570.

While the embodiment of FIG. 35 describes use of a first and secondfunctional assembly 130, a single functional assembly 130 can be used aswell. In a single functional assembly 130, the anchoring performed inStep 3560 can be performed during Step 3520 and/or during Step 3530, andmaintained through Step 3570. The method of FIG. 35 can be included inany treatment and/or diagnostic procedure as described herein.

Referring now to FIG. 36, a method of performing a medical procedureincluding expanding a functional assembly to a non-contactingconfiguration, and subsequently collapsing the intestine around thefunctional assembly is illustrated, consistent with the presentinventive concepts. The method of FIG. 36 will be described using thedevices and components of system 10 and one or more catheters 100described hereabove in reference to one or more of FIGS. 1-25. In Step3610, the distal portion of a catheter 100, including a functionalassembly 130, is inserted into the intestine of a patient, such as aninsertion through a body introduction device 50, such as an endoscope orsheath, or an insertion alongside a body introduction device 50. In someembodiments, catheter 100 is inserted over a guidewire 60. Catheter 100can be attached to console 200 of system 10. System 10 and/or catheter100 can comprise one or more sensors configured to produce a signal,such as a signal used to set and/or change one or more console settings201 of system 10.

In Step 3620, functional assembly 130 is expanded to a diameter suchthat there are gaps between the tissue contacting surface of functionalassembly 130 and the intestinal wall (e.g. the effective diameter offunctional assembly is less than the effective diameter of the lumen ofthe intestine at that location).

In Step 3630, the intestinal wall is caused to collapse aroundfunctional assembly 130, such as by applying a vacuum to a segment ofthe intestine (e.g. a segment just proximal and/or just distal tofunctional assembly 130), such as by using desufflation techniquesdescribed herein (e.g. via a port 112 or 137 of catheter 100 describedhereabove, or via a working channel of an endoscope).

In Step 3640, functional assembly 130 is activated and/or adjusted, suchas to perform a medical therapeutic and/or diagnostic procedure asdescribed herein.

The method of FIG. 36 can be constructed and arranged such that areduced number of sizes (e g diameters) of functional assemblies 130 canbe provided by system 10 to an operator (e.g. a clinician), sincesufficient contact is achieved between the intestinal wall andfunctional assembly 130 via desufflation versus expansion of functionalassembly 130. In some embodiments, system 10 comprises a kit of one ormore catheters 100, collectively comprising two or less differentdiameter functional assemblies 130, such as a single catheter 100comprising a single diameter functional assembly 130. The method of FIG.36 can be included in any treatment and/or diagnostic procedure asdescribed herein.

Referring now to FIG. 37, a method of performing a medical procedureincluding ablating tubular tissue proximate expanded tissue isillustrated, including performing the ablation based on one or morepre-tissue-expansion diameters and/or one or more post-tissue-expansiondiameters, consistent with the present inventive concepts. The method ofFIG. 37 will be described using the devices and components of system 10and one or more catheters 100 described hereabove in reference to one ormore of FIGS. 1-25. In Step 3710, the distal portion of a catheter 100,including a functional assembly 130, is inserted into the intestine of apatient, such as an insertion through a body introduction device 50,such as an endoscope or sheath, or an insertion alongside a bodyintroduction device 50. In some embodiments, catheter 100 is insertedover a guidewire 60. Catheter 100 can be attached to console 200 ofsystem 10. System 10 and/or catheter 100 can comprise one or moresensors configured to produce a signal, such as a signal used to setand/or change one or more console settings 201 of system 10.

Also in Step 3710, functional assembly 130 of catheter 100 is used tomeasure the size (e.g. one or more diameters) of a segment of intestine(e.g. an axial segment of the duodenum), such as is described herein.

In Step 3720, catheter 100 (or a second catheter 100 inserted after thecatheter of Step 3710 is removed) is used to perform tissue expansion,such as a full or near-full circumferential expansion (as describedherein) of the axial segment measured in Step 3710. The tissue expansioncan comprise injection of a fixed volume of fluid into tissue (e.g.submucosal tissue to be expanded), such as via one or more functionalelements 139 configured as needles or other fluid delivery elementsconfigured to deliver injectate 221 into tissue.

In Step 3730, catheter 100 of Step 3710 and/or 3720 is used to measurethe post-expansion size (e.g. one or more diameters) of the segment ofintestine expanded in Step 3720.

In Step 3740, catheter 100 of Step 3710, 3720, 3730 and/or a differentcatheter is used to ablate tissue (e.g. mucosal tissue) of the segmentof intestine expanded in Step 3720. In some embodiments, a catheter 100is selected based on a pre-determined diameter of an expandablefunctional assembly 130, such as a functional assembly 130 comprising anexpandable balloon 136. The selection of the diameter of the functionalassembly 130 can be based on one or more of: the diameter(s) of theintestinal segment measured in Step 3710 (pre-expansion); thediameter(s) of the intestinal segment measured in Step 3730(post-expansion); and/or both the diameter(s) measured in Step 3710 andthe diameter(s) measured in Step 3730 (e.g. based on the difference inthe two diameters). Alternatively or in addition to the selection of afunctional assembly 130 diameter based on the above, volume of fluiddelivered to functional assembly 130, pressure of fluid maintainedwithin functional assembly 130 and/or another functional assembly 130expansion parameter can be selected based on one or more of the measuredluminal diameters. For example, a volume and/or pressure of ablativefluid introduced into functional assembly 130 can be selected based onone or more of the measured luminal diameters.

Steps 3710-3740 can be repeated, such as to treat multiple axialsegments of intestinal tissue (e.g. multiple segments of the duodenum).The method of FIG. 37 can be included in any treatment and/or diagnosticprocedure as described herein.

Referring now to FIG. 38, a method of expanding a functional assembly intwo discrete steps is illustrated, consistent with the present inventiveconcepts. The method of FIG. 38 will be described using the devices andcomponents of system 10 and one or more catheters 100 describedhereabove in reference to one or more of FIGS. 1-25. Pressure, volumeand/or other system parameters can be measured by one or moresensor-based functional elements of the present inventive concepts, suchas those described hereabove. In Step 3810, the distal portion of acatheter 100, including a functional assembly 130, is inserted into theintestine of a patient such that functional assembly 130 is positionedat a first axial segment of the intestine. Catheter 100 can be insertedthrough a body introduction device 50, such as an endoscope or sheath,or inserted alongside a body introduction device 50. In someembodiments, catheter 100 is inserted over a guidewire 60. Catheter 100can be attached to console 200 of system 10. System 10 and/or catheter100 can comprise one or more sensors configured to produce a signal,such as a signal used to set and/or change one or more console settings201 of system 10 (e.g. via algorithm 251).

In Step 3820, a first volume of fluid is introduced into functionalassembly 130. The first volume can be a pre-determined volume and/ormass of fluid, or it can be a volume which is determined based on afirst threshold, such as a pressure or volume threshold, such as athreshold for the pressure generated within functional assembly 130(e.g. a pressure measured within functional assembly 130, shaft 110,connecting assembly 300 and/or console 200 by a sensor-based functionalelement of the present inventive concepts). In some embodiments, thefirst threshold comprises a pressure threshold between 0.4 psi and 1.2psi, such as between 0.6 psi and 1.0 psi.

In Step 3830, the axial segment of the intestine surrounding functionalassembly 130 is allowed to expand (e.g. a physiologic response to thepresence of functional assembly 130 and other portions of catheter 100).

In Step 3840, a second volume of fluid is introduced into functionalassembly 130, such as after a fixed time period of Step 3830 and/orafter a physiologic change in intestinal diameter occurs (e.g. expansionof the axial segment is observed for example after a time period of atleast 15 seconds, at least 30 seconds, at least 1 minute, or at least 2minutes).

The method of FIG. 38 can be performed prior to a luminal sizingprocedure, a tissue expansion procedure and/or a tissue ablationprocedure as described herein. In some embodiments, a luminal sizingprocedure is performed to determine any of the thresholds describedhereabove. Steps 3810-3840 can be repeated, such as to treat and/ordiagnose multiple axial segments of intestinal tissue (e.g. multiplesegments of the duodenum).

Referring now to FIG. 39, a method of expanding a functional assemblybased on two pressure thresholds is illustrated, consistent with thepresent inventive concepts. The method of FIG. 39 will be describedusing the devices and components of system 10 and one or more catheters100 described hereabove in reference to one or more of FIGS. 1-25. InStep 3910, the distal portion of a catheter 100, including a functionalassembly 130, is inserted into the intestine of a patient such thatfunctional assembly 130 is positioned at a first axial segment of theintestine. Catheter 100 can be inserted through a body introductiondevice 50, such as an endoscope or sheath, or inserted alongside a bodyintroduction device 50. In some embodiments, catheter 100 is insertedover a guidewire 60. Catheter 100 can be attached to console 200 ofsystem 10. System 10 and/or catheter 100 can comprise one or moresensors configured to produce a signal, such as a signal used to setand/or change one or more console settings 201 of system 10.

Also in Step 3910, fluid is introduced into functional assembly 130until a first threshold is reached (e.g. a first pressure thresholdrelated to pressure measured within functional assembly 130, shaft 110,connecting assembly 300 and/or console 200).

In Step 3920, pressure within functional assembly 130 is measured andcompared to a second threshold (e.g. a second pressure threshold lessthan the first pressure threshold). Alternatively or additionally,pressure of a different portion of system 10 can be measured, such as apressure of a fluid line or reservoir in fluid communication withfunctional assembly 130 (e.g. a pressure within shaft 110, connectingassembly 300 and/or console 200).

If the measured pressure falls below the second pressure threshold, Step3910 is repeated, introducing more fluid into functional assembly 130until a third pressure threshold is reached (e.g. a third pressurethreshold of similar pressure level to the first pressure threshold).

If the pressure measured in Step 3920 does not fall below the secondpressure threshold, Step 3930 is performed,

In Step 3930, completion of a first time period is checked, such as thetime since initially introducing fluid into functional assembly 130, thetime since first achieving the first pressure threshold, or other timeperiod. If the time period is not completed, Step 3920 is performedagain. If the time period is completed, Step 3940 is performed.

In Step 3940, functional assembly 130, in its expanded state thatresults from Steps 3910-3930, is used to perform a diagnostic procedure(e.g. luminal diameter measurement procedure) and/or a treatmentprocedure (e.g. a tissue expansion procedure and/or a tissue ablationprocedure).

Steps 3910-3940 can be repeated, such as to treat and/or diagnosemultiple axial segments of intestinal tissue (e.g. multiple segments ofthe duodenum). In some embodiments, functional assembly 130, Step 3920is repeated and pressure is monitored (e.g. for a second time period).If pressure falls below a fourth pressure threshold (e.g. a fourthpressure threshold similar to the second pressure threshold), a thirdvolume of fluid can be introduced into functional assembly 130. Thethird volume of fluid can be delivered until a fifth pressure thresholdis reached, such as a fifth pressure threshold similar to the firstpressure threshold and/or the third pressure threshold.

Referring now to FIG. 40, a method of causing a functional assembly tocontact wall tissue of a segment of the intestine is illustrated,consistent with the present inventive concepts. The method of FIG. 40will be described using the devices and components of system 10 and oneor more catheters 100 described hereabove in reference to one or more ofFIGS. 1-25. In Step 4010, the distal portion of a catheter 100,including an expandable functional assembly 130, is inserted into theintestine of a patient such that functional assembly 130 is positionedat a first axial segment of the intestine. Catheter 100 can be insertedthrough a body introduction device 50, such as an endoscope or sheath,or inserted alongside a body introduction device 50. In someembodiments, catheter 100 is inserted over a guidewire 60. Catheter 100can be attached to console 200 of system 10. System 10 and/or catheter100 can comprise one or more sensors configured to produce a signal,such as a signal used to set and/or change one or more console settings201 of system 10 (e.g. via algorithm 251).

Also in Step 4010, a first volume of fluid is introduced into functionalassembly 130. For example, the first volume of fluid can be a fluidvolume that causes a sufficient or otherwise pre-determined level ofapposition between a balloon 136 of functional assembly 130 and theluminal wall of the axial segment of the intestine. The first volume offluid can be a fluid volume that causes the pressure within functionalassembly 130 to reach a threshold.

In Step 4020, the volume of fluid in functional assembly 130 is changedto a second volume, different than the first volume. In someembodiments, the second volume is less than the first volume (i.e. fluidis extracted from functional assembly 130 in Step 4020). In otherembodiments, the second volume is greater than the first volume (i.e.fluid is added to functional assembly 130).

In Step 4030, the intestinal wall is contracted, such as by using one ormore desufflation techniques as described herein. In some embodiments,such as when fluid is extracted from functional assembly 130 in Step4020, contraction of the intestinal wall causes the intestinal wall tomake contact with functional assembly 130. In other embodiments, such aswhen fluid is added to functional assembly 130 in Step 4030, contractionof the intestinal wall causes increased contact between the intestinalwall and functional assembly 130.

In Step 4040, a treatment (e.g. an ablation treatment or other treatmentas described herein) is performed upon the axial segment of theintestinal wall in contact with functional assembly 130 (and neighboringtissue as described herein).

The method of FIG. 40 can be used to accurately control the amount ofcontact between functional assembly 130 and the luminal wall of an axialsegment of the intestine and/or to precisely control the timing ofcontact between functional assembly 130 and the luminal wall.

Steps 4010-4040 can be repeated, such as to treat and/or diagnosemultiple axial segments of intestinal tissue (e.g. multiple segments ofthe duodenum).

Referring now to FIG. 41, a method of performing a tissue treatment thatincludes activating a functional assembly based on an image isillustrated, consistent with the present inventive concepts. The methodof FIG. 41 will be described using the devices and components of system10 and one or more catheters 100 described hereabove in reference to oneor more of FIGS. 1-25. In Step 4110, the distal portion of a catheter100, including a functional assembly 130, is inserted into the intestineof a patient such that functional assembly 130 is positioned at a firstaxial segment of the intestine. Catheter 100 can be inserted through abody introduction device 50, such as an endoscope or sheath, or insertedalongside a body introduction device 50. In some embodiments, catheter100 is inserted over a guidewire 60. Catheter 100 can be attached toconsole 200 of system 10. System 10 and/or catheter 100 can comprise oneor more sensors configured to produce a signal, such as a signal used toset and/or change one or more console settings 201 of system 10.

In some embodiments, functional assembly 130 is at least partiallyexpanded (e.g. via a fluid introduced into a balloon of functionalassembly 130 or via a mechanical linkage configured to radially deploy aportion of functional assembly 130) within the first axial segment ofthe intestine in Step 4110.

In Step 4120, one or more images are captured, such as by camera 52 ofintroduction device 50 (e.g. a camera of an endoscope), by imagingdevice 55 and/or another imaging device of system 10. The one or moreimages can comprise an image including patient tissue, functionalassembly 130 and/or another component of system 10. The one or morecaptured images are analyzed, such as an analysis performed manually(e.g. by a clinician) and/or automatically (e.g. by one or more imageprocessing algorithms of system 10, such as algorithm 251). In someembodiments, the image capture by camera 52 and/or imaging device 55(e.g. and analyzed by algorithm 251) comprises an image selected fromthe group consisting of: a spectroscopy image, such as a Ramanspectroscopy or other image configured to identify denatured proteins; afluorescence image, such as a time-resolved fluorescence image; opticalcoherence tomography (OCT) image; ultrasound image; ultrasonicelastography image; colorimetry image; confocal endomicroscopy image;and combinations of one or more of these. In some embodiments, injectate221 is present in tissue, and a color change or fluorescence is detectedwhen injectate 221 is heated.

In Step 4130, the results of the image analysis performed in Step 4120are compared to a level of acceptability. If an acceptable level isachieved, the method of FIG. 41 continues in Step 4140. If an acceptablelevel is not achieved, Step 4180 a is performed in which the firsttreatment is aborted or modified. Unacceptable levels of acceptabilitycan include images which identify improper positioning of functionalassembly 130 such as positioning of functional assembly proximatenon-target tissue (e.g. the ampulla of Vater); improper expansion offunctional assembly 130; improper position of one or more fluid deliveryelements 139 c; presence of diseased tissue proximate functionalassembly 130 or otherwise; presence of infected tissue proximatefunctional assembly 130 or otherwise; and combinations of one or more ofthese.

Aborting the first treatment in Step 4180 a can comprise removingcatheter 100 (and potentially one or more of devices of system 10) fromthe patient.

Modifying the first treatment in Step 4180 a can comprise returning tostep 4110 in which functional assembly 130 is repositioned in theintestine and/or another adjustment is made based on the unacceptableresults of the image analysis of Step 4130.

In Step 4140, functional assembly 130 is activated (e.g. energy isdelivered to tissue such as heat delivered from hot fluid, RF energy isdelivered by one or more electrode-based functional elements 139, lightenergy is delivered by one or more optical component-based functionalelements 139, and/or other energy is delivered as described herein).

In Step 4150, one or more images are captured, such as by camera 52 ofintroduction device 50 (e.g. a camera of an endoscope), by imagingdevice 55 and/or another imaging device of system 10. The one or moreimages can comprise an image including patient tissue, functionalassembly 130 and/or another component of system 10. The one or morecaptured images are analyzed, such as an analysis performed manually(e.g. by a clinician) and/or automatically (e.g. by one or more imageprocessing algorithms of system 10, such as algorithm 251).

In Step 4160, the results of the image analysis performed in Step 4150are compared to a level of acceptability. If an acceptable level isachieved, the method of FIG. 41 continues in Step 4170. If an acceptablelevel is not achieved, Step 4180 b is performed in which the firsttreatment is aborted or modified. Unacceptable levels of acceptabilitycan include images which identify: inadequate expansion of tissue;inadequate treatment of target tissue; undesired treatment of targettissue; adverse effects upon non-target tissue; improper positioning offunctional assembly 130 such as positioning of functional assemblyproximate non-target tissue (e.g. the ampulla of Vater); improperexpansion of functional assembly 130; improper position of one or morefluid delivery elements 139 c; presence of diseased tissue proximatefunctional assembly 130 or otherwise; presence of infected tissueproximate functional assembly 130 or otherwise; and combinations of oneor more of these.

Aborting the first treatment in Step 4180 b can comprise removingcatheter 100 (and potentially one or more of devices of system 10) fromthe patient.

Modifying the first treatment in Step 4180 b can comprise returning toStep 4110 in which functional assembly 130 is repositioned in theintestine and/or another adjustment is made based on the unacceptableresults of the image analysis of Step 4130.

Alternatively, modifying the first treatment in Step 4180 b can comprisereturning to Step 4140 (as shown in FIG. 41), in which functionalassembly 130 is reactivated, to deliver additional (similar ordissimilar) energy to tissue.

In Step 4170, an assessment of first treatment completeness isperformed. The assessment can be performed manually (e.g. by aclinician) and/or automatically (e.g. by one or more algorithms ofsystem 10, such as via one or more images produced as described herein).If it is determined that the first treatment is not complete, Step 4140and subsequent steps are repeated, such as to deliver additional energyto tissue. If it is determined that the first treatment is complete,Step 4190 is performed in which the first treatment is ended. In someembodiments, Step 4190 comprises overall completion of a patientprocedure, such as when catheter 100 and/or other components of system10 are removed from the patient. In other embodiments, the steps of themethod of FIG. 41 are repeated for a second treatment, such as byrepeating Step 4110 at a second axial segment of intestinal tissue andcontinuing with the subsequent steps. In some embodiments, at least 2 orat least 3 axial segments of axial segments of duodenal tissue aretreated, such as is described herein to treat diabetes.

Referring now to FIG. 42, a method of performing a tissue treatmentbased on the geometry of the intestine is illustrated, consistent withthe present inventive concepts. The method of FIG. 42 will be describedusing the devices and components of system 10 and one or more catheters100 described hereabove in reference to one or more of FIGS. 1-25. InStep 4210, the narrowest segment of a portion of the intestine (e.g. thenarrowest portion of a duodenal or other intestinal segment to betreated) is identified, and one or more diameters (e.g. the narrowestdiameter) are measured. The identification of the narrowest segmentand/or the diameters can be measured by a component of system 10, suchas catheter 100, camera 52 of introduction device 50, and/or imagingdevice 55. In some embodiments, the identification and measurement areperformed in the same clinical procedure as the tissue expansion andablation performed subsequently in Steps 4220 through 4270.Alternatively, the identification and measurement are performed in aseparate procedure, such as an imaging procedure (e.g. an ultrasound, Ctscan or MRI procedure), which can be performed at an earlier date.

In Step 4220, a first catheter 100 a is selected based on anablation-based functional assembly 130 a that is appropriate for the(narrowest) diameters measured in Step 4210. For example, system 10 caninclude multiple catheters 100 each with a functional assembly 130 awith a different expanded diameter. The selection performed in Step 4220provides a functional assembly 130 a with an appropriate diameter toavoid excessive force being exerted between functional assembly 130 aand the narrowest segment of the intestine being treated (e.g. during anenergy delivery or other ablation step). The diameter of theablation-based functional assembly 130 a selected can be approximatelyequal to, slightly larger than or slightly smaller than the narrowestdiameter measured, such as to provide adequate ablation (e.g. in Step4270 described herebelow) of one or more inner layers of the intestine(e.g. all of the mucosal layer and a partial inner sublayer of thesubmucosal layer), without damaging outer layers of the intestine (e.g.the serosal layer).

In Step 4230, a second catheter 100 b comprising a functional assembly130 b configured for tissue expansion is selected. In some embodiments,the second catheter 100 b is the same catheter as first catheter 100 a(e.g. its functional assembly 130 b is configured to both ablate tissueand expand tissue or the catheter 100 a comprises two separatefunctional assemblies 130 a and 130 b, such as are described herein). Insome embodiments, the second catheter 100 b comprises a functionalassembly 130 b that is selected based on the diameter measurementsperformed in Step 4210 (e.g. to be compatible with the narrowestdiameter of the intestinal segment to be treated).

The second catheter 100 b is inserted into the intestine of a patientsuch that its functional assembly 130 b is positioned at a first axialsegment of the intestine. Second catheter 100 b can be inserted througha body introduction device 50, such as an endoscope or sheath, orinserted alongside a body introduction device 50. In some embodiments,second catheter 100 b is inserted over a guidewire 60. Second catheter100 b can be attached to console 200 of system 10. System 10 and/orsecond catheter 100 b can comprise one or more sensors configured toproduce a signal, such as a signal used to set and/or change one or moreconsole settings 201 of system 10. In some embodiments, the firstcatheter 100 a and/or second catheter 100 b are used to measure theintestinal lumen diameters in step 4210 or otherwise.

Also in Step 4230, functional assembly 130 b is expanded, such as bydelivering gas or another fluid into functional assembly 130 b until itsdiameter achieves a predetermined size and/or until a sufficientapposition with tissue is achieved (e.g. as determined by a pressuremeasurement and/or direct visualization as described herein).

In Step 4240, vacuum can be applied to the second catheter 100 b, suchas a vacuum delivered to one or more ports 137 of functional assembly130 b. The applied vacuum can engage each port 137 with tissue or atleast bring tissue into proximity with each port 137. In someembodiments, the applied vacuum causes tissue to enter the associatedport 137. In some embodiments, the applied vacuum is configured to causeone or more fluid delivery elements 139 c to move closer to, engage withand/or penetrate tissue (e.g. tissue captured within a port 137).

In Step 4250, injectate 221 is delivered into tissue (e.g. submucosaltissue), such as until the pressure within functional assembly 130 breaches a threshold. Alternatively, a fixed amount of injectate 221 isdelivered into tissue, or injectate 221 is delivered into tissue untilan acceptable image of tissue expansion is visualized (e.g. via camera52 of introduction device 50 and/or imaging device 55 as describedherein). In some embodiments, the volume of air or other fluid deliveredinto functional assembly 130 b during Step 4230 (to expand functionalassembly 130 b), is adjusted (e.g. decreased) during the delivery ofinjectate 221 into tissue. The adjustment of the fluid within functionalassembly 130 can be based on a measured pressure (e.g. that increases astissue expands) and/or the amount of injectate delivered into tissue.Adjustment (e.g. decrease) of fluid within functional assembly 130 b canbe performed to avoid excessive force being applied to tissue and/or toallow proper tissue expansion (e.g. proper expansion of one or morelayers of submucosal tissue).

In Step 4260, functional assembly 130 b is disengaged from tissue (e.g.vacuum is removed from one or more ports 137 and/or one or more fluiddelivery elements 139 c are retracted or otherwise disengaged fromtissue), and functional assembly 130 b is radially collapsed. Secondcatheter 100 b can be removed from the patient, repositioned, and/orremain in place (e.g. when first catheter 100 a and second catheter 100b comprise the same catheter).

In Step 4270, a functional assembly 130 a of catheter 100 a ispositioned at or near the first axial segment of intestine (herein “atthe first axial segment of intestine”) and tissue of the first axialsegment is ablated (i.e. tissue proximate the tissue expanded in Step4250). First catheter 100 a can be inserted through a body introductiondevice 50, such as an endoscope or sheath, or inserted alongside a bodyintroduction device 50. In some embodiments, first catheter 100 a isinserted over a guidewire 60. As described above, catheter 100 a andcatheter 100 b can comprise the same catheter, avoiding the need toposition a second catheter at the first axial segment. First catheter100 a can be attached to console 200 of system 10. System 10 and/orfirst catheter 100 a can comprise one or more sensors configured toproduce a signal, such as a signal used to set and/or change one or moreconsole settings 201 of system 10.

Also in Step 4270, functional assembly 130 a is activated to ablatetissue of the first axial segment of intestine, such as by deliveringthermal or other energy provided by console 200 to tissue, as describedherein.

The tissue expansion procedure performed in steps 4230 through 4260 canbe repeated at multiple axial segments of intestine. In someembodiments, a series of multiple tissue expansions are followed by acorresponding series of ablation steps of Step 4270 (e.g. ablating thesame or a different quantity of axial segments of intestine).Alternatively, a single tissue expansion (Steps 4230 through 4260) at afirst segment of intestine is followed by a single ablation Step 4270performed at the same first segment. Subsequently, similar tissueexpansion can be performed at one or more additional segments of theintestine (e.g. a second, third, etc). Ablation of Step 4270 can beperformed soon after each tissue expansion of Steps 4230 through 4260(e.g. in an alternating fashion of tissue expansion of a segmentfollowed by ablation of that segment).

Referring now to FIG. 43, a method of marking tissue and performing atissue treatment based on the tissue marking is illustrated, consistentwith the present inventive concepts. The method of FIG. 43 will bedescribed using the devices and components of system 10 and one or morecatheters 100 described hereabove in reference to one or more of FIGS.1-25. In Step 4310, a patient is selected for treatment by the systems,methods and devices of the present inventive concepts, such as adiabetic patient selected for ablation of duodenal mucosa.

In Step 4320, the distal portion of a catheter 100, including afunctional assembly 130, is inserted into the intestine of a patientsuch that functional assembly 130 is positioned at a first axial segmentof the intestine. Catheter 100 can be inserted through a bodyintroduction device 50, such as an endoscope or sheath, or insertedalongside a body introduction device 50. In some embodiments, catheter100 is inserted over a guidewire 60. Catheter 100 can be attached toconsole 200 of system 10. System 10 and/or catheter 100 can comprise oneor more sensors configured to produce a signal, such as a signal used toset and/or change one or more console settings 201 of system 10.

In Step 4330, one or more portions of tissue are marked and/oridentified. In some embodiments, Step 4330 is performed prior to Step4320. In some embodiments, the tissue marking and/or identification ofStep 4330 is performed with catheter 100 and/or another component ofsystem 10, such as tool 500 as described hereabove. Tissue marking cancomprise implantation of a temporary marker, or marking of tissue with atattoo or other tissue dyeing procedure, such as using marker 430, alsodescribed hereabove. In some embodiments, marked tissue comprises tissueselected from the group consisting of: target tissue; non-target tissue;tissue proximate non-target tissue (e.g. tissue proximate the ampulla ofVater or tissue proximate the pylorus); safety margin tissue; diseasedtissue; healthy tissue; and combinations of one or more of these.

In Step 4340, target tissue is treated (e.g. target tissue comprisingdiseased tissue or otherwise adversely functioning tissue) withfunctional assembly 130 of catheter 100, such as a target tissuetreatment comprising tissue ablation; tissue expansion; tissue expansionand ablation; and combinations of one or more of these. The treatment oftarget tissue is performed at a location selected based on the tissueidentification and/or marking performed in Step 4330.

For example, in procedures treating mucosa of the duodenum, one or moremarkings can be made to prevent adversely affecting the ampulla of Vater(e.g. by preventing energy deliver to tissue within 1.5 cm, 1.0 cm or0.5 cm of the ampulla of Vater) and/or to ensure treatment of tissue(e.g. mucosal tissue) within 5 cm, within 10 cm or within 15 cm of theampulla of Vater.

In Step 4350, catheter 100 is removed. The markers may be removed, orleft in place (e.g. when a dye is used or when a deployed marker isconstructed and arranged to pass through the GI system naturally).

While the preferred embodiments of the devices and methods have beendescribed in reference to the environment in which they were developed,they are merely illustrative of the principles of the inventions.Modification or combinations of the above-described assemblies, otherembodiments, configurations, and methods for carrying out the invention,and variations of aspects of the invention that are obvious to those ofskill in the art are intended to be within the scope of the claims. Inaddition, where this application has listed the steps of a method orprocedure in a specific order, it may be possible, or even expedient incertain circumstances, to change the order in which some steps areperformed, and it is intended that the particular steps of the method orprocedure claim set forth below not be construed as being order-specificunless such order specificity is expressly stated in the claim.

What is claimed is:
 1. A method for performing a medical procedure in anintestine of a patient, comprising: selecting a patient diagnosed withat least one of non-alcoholic fatty liver disease (NAFLD) ornon-alcoholic steatohepatitis (NASH); providing a system comprising: acatheter for insertion into the intestine, the catheter comprising: anelongate shaft comprising a distal portion; and a functional assemblypositioned on the shaft distal portion and comprising at least onetreatment element; introducing the catheter into the patient diagnosedwith at least one of NAFLD or NASH; and treating target tissue with theat least one treatment element, wherein the target tissue comprisesmucosal tissue of the patient's small intestine; wherein the medicalprocedure is configured to treat the at least one of NAFLD or NASH: andwherein the patient had elevated baseline levels of aspartatetransaminase (AST) and alanine transaminase (ALT) indicative ofinflammation of the liver prior to treating the target tissue with theat least one treatment element, the patient achieves a reduction in theelevated baseline levels of AST and ALT after treatment, and the patientachieves the reduction in the levels of AST and ALT by 24 weeks aftertreatment and sustains the reduction through week 48 after treatment. 2.The method according to claim 1, wherein the medical procedure isfurther configured to treat insulin resistance.
 3. The method accordingto claim 1, wherein the medical procedure is further configured to treata disease or disorder selected from the group consisting of: Type 2diabetes; Type 1 diabetes; “Double diabetes”; gestational diabetes;hyperglycemia; pre-diabetes; impaired glucose tolerance; insulinresistance; and combinations thereof.
 4. The method according to claim1, wherein treating target tissue modifies at least one of nutrientabsorption by the target tissue, hormonal signaling from the targettissue, or secretions of the target tissue.
 5. The method according toclaim 1, wherein treating target tissue comprises treating mucosaltissue within 15 cm of the patient's ampulla of Vater.
 6. The methodaccording to claim 1, wherein the method comprises avoiding treatingtissue between a first location proximate the patient's ampulla of Vaterand a second location 0.5 cm distal to the patient's ampulla of Vater.7. The method according to claim 1, wherein at least 6 cm of length ofthe patient's duodenum are treated.
 8. The method according to claim 1,wherein at least 9 cm of length of the patient's duodenum are treated.9. The method according to claim 1, wherein treating target tissuecomprises treating at least a first axial segment and a second axialsegment of the intestine.
 10. The method according to claim 1, whereintreating target tissue comprises treating between two and six axialsegments of the intestine to treat at least 6 cm of axial length ofintestine.
 11. The method according to claim 1, wherein treating targettissue comprises treating an amount of tissue that is based on theseverity of the patient's NAFLD and/or NASH.
 12. The method according toclaim 1, further comprising identifying non-target tissue, wherein thenon-target tissue is identified by marking tissue selected from thegroup consisting of: ampulla of Vater; tissue proximate the ampulla ofVater; pylorus; tissue proximate the pylorus; and combinations thereof.13. The method according to claim 1, wherein treating target tissuecomprises a series of tissue ablation steps, each comprising ablation ofan axial length of intestinal tissue, wherein each ablation step ispreceded by a tissue expansion step.
 14. The method according to claim13, further comprising preventing axial motion of the functionalassembly between the tissue expansion and the tissue treatment steps.15. The method according to claim 13, further comprising applying vacuumto tissue during the tissue expansion step.
 16. The method according toclaim 1, wherein treating target tissue comprises a series of tissueablation steps, each ablation step comprising ablation of an axiallength of intestinal tissue, wherein each ablation step is followed by atissue neutralizing step.
 17. The method according to claim 16, whereineach ablation step comprises a heat ablation of tissue and eachneutralizing step comprises a cooling of tissue.
 18. The methodaccording to claim 16, further comprising performing a separate tissueneutralizing step prior to each ablation step.
 19. The method accordingto claim 18, wherein each ablation step comprises a heat ablation oftissue and each separate neutralizing step comprises a cooling oftissue.
 20. The method according to claim 1, further comprisingmaintaining the functional assembly at or below a target diameter, atarget pressure, or a target volume.
 21. The method according to claim1, further comprising delivering an anti-peristaltic agent.
 22. Themethod according to claim 1, further comprising modifying a pressure ofa segment of intestine that is proximate the target tissue beingtreated.
 23. The method according to claim 1, wherein the functionalassembly includes a tissue contacting portion comprising a surface areabetween 500 mm² and 3500 mm².
 24. The method according to claim 1, wherethe functional assembly comprises an expanded diameter between 19 mm and28 mm.
 25. The method according to claim 1, wherein the patient had atleast 3 cm of mucosal tissue treated.
 26. The method according to claim25, wherein the mucosal tissue comprises duodenal mucosal tissue. 27.The method according to claim 1, wherein the patient baseline AST levelis above 50 mg/dL and is below 40 mg/dl at weeks 24 and 48 aftertreatment.
 28. The method according to claim 1, wherein the patientbaseline ALT level is above 40 mg/dL and is below 30 mg/dl at weeks 24and 48 after treatment.